Affinage

HLA-E

HLA class I histocompatibility antigen, alpha chain E · UniProt P13747

Length
358 aa
Mass
40.1 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-E is a non-classical MHC class I molecule that functions as a central sensor of cellular integrity, assembling as a β2-microglobulin-associated complex that requires high-affinity peptide loading—predominantly nonameric leader-sequence (VL9) peptides derived from classical HLA class Ia and HLA-G signal sequences—for stable cell-surface expression (PMID:3260916, PMID:9700506, PMID:37264229). Surface stabilization is strictly dependent on β2-microglobulin availability, TAP-mediated transport of leader peptides into the ER, and the allelic identity at position 107 governing thermal stability and surface levels (PMID:10064069, PMID:10887053, PMID:12411439, PMID:12618909). At the cell surface, HLA-E primarily engages the CD94/NKG2 receptor family on NK cells and T cell subsets: it is the dominant ligand for the inhibitory CD94/NKG2A receptor, whose engagement protects target cells from NK-mediated lysis, and for the activating CD94/NKG2C receptor, with the receptor-bound outcome dictated by the precise conformation of the peptide within the binding groove rather than by heavy-chain allelic differences (PMID:9486650, PMID:9560253, PMID:15728498, PMID:18339401). Because peptide supply links HLA-E surface display to the status of classical class I expression, this axis allows NK cells to detect downregulation of HLA class Ia in infected or transformed cells (PMID:10887053, PMID:12618909). HLA-E additionally presents lower-affinity pathogen-derived peptides—from HCMV, EBV, HIV, Mycobacterium tuberculosis, and SARS-CoV-2—to αβ TCR-bearing CD8+ T cells and to adaptive/memory NK cells, with non-VL9 peptides adopting alternative groove conformations that reconfigure the receptor- and TCR-interacting α2 region (PMID:11920559, PMID:35705051, PMID:28676677, PMID:33766848, PMID:35235832, PMID:38064568, PMID:37390223). HLA-E trafficking is distinct from classical class I: limited high-affinity peptide causes ER retention, and its cytoplasmic tail drives rapid surface internalization into late and recycling endosomes, a feature exploited by HIV-1 Nef to downmodulate surface HLA-E (PMID:37140910, PMID:31375574, PMID:26310830). Its expression is transcriptionally induced by IFN-γ via STAT1 and by CIITA, but not by NF-κB or IRF1, and is upregulated on endothelial cells, senescent cells, and tumor cells where the HLA-E:NKG2A interaction acts as an immune checkpoint suppressing NK and CTL responses (PMID:11137213, PMID:17179229, PMID:31160572, PMID:21670276, PMID:36706761).

Mechanistic history

Synthesis pass · year-by-year structured walk · 35 steps
  1. 1988 High

    Established that the HLA-E locus encodes a genuinely expressible MHC class I protein rather than a pseudogene, fixing it as a candidate immune molecule.

    Evidence gene transfer into class I-null lymphoblastoid cells with immunoprecipitation detecting β2m association, and deletion mapping on chromosome 6

    PMID:3260916

    Open questions at the time
    • Did not define what peptides HLA-E presents
    • No receptor or functional role identified
    • Tissue distribution and induction unknown
  2. 1998 High

    Defined the core function of HLA-E by showing it is the predominant ligand for CD94/NKG2 receptors and that its surface display inhibits NK cytotoxicity, explaining how missing-self surveillance is licensed.

    Evidence HLA-E tetramer binding to NKG2A/B/C transfectants, peptide-loaded .221 transfectants, antibody blocking, and NK cytotoxicity assays

    PMID:9486650 PMID:9560253

    Open questions at the time
    • Did not quantify differential affinities of activating vs inhibitory receptors
    • Structural basis of peptide-dependent recognition unresolved
    • Did not address TCR-mediated recognition
  3. 1998 Medium

    Showed the HLA-E groove is uniquely specialized for conserved leader-sequence peptides with high specificity along the entire peptide, distinguishing it from promiscuous class Ia molecules.

    Evidence structural analysis citing crystallographic data (review framework)

    PMID:9700506

    Open questions at the time
    • Single review-derived structural claim in this corpus
    • Did not establish which peptide features control receptor recognition
  4. 2000 Medium

    Linked HLA-E surface expression to the TAP peptide-supply pathway, establishing the mechanistic logic by which NK cells sense loss of classical class I presentation.

    Evidence review synthesis of crystallographic and cell-biology experiments on TAP dependency

    PMID:10887053

    Open questions at the time
    • Review synthesis rather than primary data in this entry
    • Quantitative peptide affinity thresholds not defined
  5. 1999 High

    Demonstrated that β2-microglobulin availability and the position-107 allelic substitution govern HLA-E assembly, transport, and surface levels, identifying biochemical bottlenecks in its display.

    Evidence transfection of HLA-E ± human β2m into mouse myeloma cells with thermal stability assays and FACS quantification

    PMID:10064069

    Open questions at the time
    • Did not connect surface levels to receptor recognition outcomes
    • In vivo relevance of allelic effect untested here
  6. 2000 High

    Extended HLA-E function to a physiological context by showing trophoblast HLA-E inhibits decidual NK cytotoxicity via CD94/NKG2, implicating it in maternal-fetal tolerance.

    Evidence HLA-E tetramer staining of decidual NK cells, anti-CD94 blocking, and primary-cell cytotoxicity assays

    PMID:10898498

    Open questions at the time
    • Did not identify the in vivo peptide presented by trophoblast HLA-E
    • Did not address activating receptor outcomes
  7. 2000 Medium

    Identified the transcriptional control of HLA-E, showing IFN-γ/STAT1 and CIITA induction but insensitivity to NF-κB and IRF1, distinguishing its regulation from inflammatory induction.

    Evidence promoter reporter assays and cis-element mapping

    PMID:11137213

    Open questions at the time
    • Single-lab promoter analysis
    • Did not characterize regulation in primary tissue contexts
  8. 2002 High

    Showed that HLA-E allelic variants differ in peptide affinity and stability but adopt indistinguishable heavy-chain conformations, separating expression-level effects from structural effects.

    Evidence crystal structures of HLA-E(G) with two peptides plus thermal stability, affinity, and surface expression measurements

    PMID:12411439

    Open questions at the time
    • Did not test receptor-binding consequences of allelic differences directly
    • Peptide repertoire breadth not assessed
  9. 2002 High

    Established a second recognition arm by showing HLA-E can be recognized directly by αβ TCRs on CD8+ T cells independently of CD94/NKG2C, including a viral (EBV BZLF-1) peptide.

    Evidence CTL cytotoxicity with anti-TCR vs anti-CD94 blocking and TCR-dependent HLA-E tetramer staining

    PMID:11920559

    Open questions at the time
    • TCR diversity and peptide breadth not defined
    • In vivo protective role untested
  10. 2003 Medium

    Connected HLA-E surface levels to free cytoplasmic β2m in tumor cells, showing class Ia downregulation can paradoxically raise HLA-E and shape NK evasion.

    Evidence antibody staining of tumor lines with defined HLA alterations and exogenous β2m supplementation

    PMID:12618909

    Open questions at the time
    • Single-lab correlative cell-line study
    • Functional NK outcome of increased HLA-E not directly tested here
  11. 2005 High

    Quantified the biophysical hierarchy of CD94/NKG2 receptor binding and demonstrated peptide identity—not allelic variation—controls receptor affinity, defining the molecular tuning of HLA-E signalling.

    Evidence quantitative affinity and thermodynamic measurements for NKG2A/C/E with HLA-E/peptide complexes

    PMID:15728498

    Open questions at the time
    • Did not resolve how peptide alters the recognition interface structurally
    • Functional NK consequences inferred not directly measured here
  12. 2005 High

    Validated peptide-dependent HLA-E function in a xenogeneic context and engineered a single-chain trimer, providing a reagent and proof that loaded HLA-E suffices to inhibit NK responses.

    Evidence porcine cell transfection, NK cytotoxicity and IFN-γ assays, and single-chain β2m-peptide-HLA-E construct

    PMID:15829309

    Open questions at the time
    • SCT may not capture native conformational dynamics
    • Restricted to inhibitory receptor readouts
  13. 2007 High

    Demonstrated cytokine-driven HLA-E upregulation on endothelium and release of soluble HLA-E, extending its immunomodulatory reach to bystander protection.

    Evidence cytokine stimulation of endothelial cells, flow cytometry, NK cytotoxicity, and sHLA-E ELISA

    PMID:17179229

    Open questions at the time
    • Mechanism of sHLA-E generation not defined
    • In vivo significance of soluble form untested
  14. 2008 High

    Provided the structural basis for differential receptor recognition by showing subtle peptide conformational changes in the groove—not heavy-chain changes—dictate CD94/NKG2 binding.

    Evidence X-ray crystallography of HLA-E with HLA-Cw*07 and HLA-G*01 leader peptides at 2.5 Å

    PMID:18339401

    Open questions at the time
    • Limited to two leader peptides
    • Did not address pathogen-peptide conformations
  15. 2011 Medium

    Showed HLA-E:NKG2A acts as a functional checkpoint in tumors, neutralizing the survival benefit of CTL infiltration and implicating it in cancer immune evasion.

    Evidence immunohistochemistry on 420 tumor sections with in situ NKG2A+ CTL detection and survival analysis

    PMID:21670276

    Open questions at the time
    • Functional inhibition inferred from survival rather than direct in vitro blocking
    • Peptides presented in tumor context not identified
  16. 2014 High

    Defined the HLA-E:NKG2C axis as a driver of HCMV-induced adaptive NK cell expansion requiring monocyte-derived IL-12, linking HLA-E to NK memory formation.

    Evidence NK-monocyte coculture, NKG2C blockade, HLA-E siRNA in infected fibroblasts, and IL-12 neutralization

    PMID:25384219

    Open questions at the time
    • Specific HLA-E peptide driving expansion not pinpointed here
    • Durability of memory not assessed
  17. 2015 Medium

    Distinguished the peptide selectivity of inhibitory versus activating signalling, showing nearly all peptides inhibit via NKG2A while only restricted peptides (notably HLA-G leader) activate NKG2C, with HLA-E:G triggering lysosomal NKG2C internalization.

    Evidence degranulation (CD107a) assays with a peptide panel and bafilomycin-sensitive NKG2C internalization assays

    PMID:26382247

    Open questions at the time
    • Single-lab functional dataset
    • Structural basis of activating peptide selectivity not resolved here
  18. 2015 Medium

    Revealed that during macrophage differentiation HLA-E is preferentially routed into autophagy-lysosomal vesicles rather than the surface, indicating cell-state-specific trafficking control.

    Evidence confocal LC3/LAMP1 colocalization, subcellular fractionation, flow cytometry, and NK cytotoxicity in monocytic cells

    PMID:26310830

    Open questions at the time
    • Functional purpose of intracellular HLA-E pool unclear
    • Single-lab study
  19. 2017 Medium

    Showed HLA-E can present post-translationally modified (O-mannosylated) mycobacterial glycopeptides to CD8+ T cells, expanding the chemical space of HLA-E antigens.

    Evidence T cell clone recognition assays, HLA-E tetramers, Rv1002c mannosyltransferase mutant bacteria, and synthetic glycopeptides

    PMID:28676677

    Open questions at the time
    • Single clone/single-lab evidence
    • In vivo protective relevance untested
  20. 2018 High

    Demonstrated structurally that pathogen-derived peptides occupy the HLA-E groove with greater anchor-residue tolerance and alternative conformations than canonical VL9, broadening the predicted HLA-E pathogen peptidome.

    Evidence X-ray crystallography of HLA-E/HIV and Mtb peptide complexes with pocket mutagenesis and binding studies

    PMID:30087334

    Open questions at the time
    • Receptor/TCR consequences of these conformations not directly measured here
    • Limited peptide set
  21. 2018 High

    Showed adaptive NK cells discriminate HLA-E peptide complexes with exquisite specificity via NKG2C, with the HLA-G leader peptide selectively enriching functionally superior adaptive NK cells.

    Evidence NK coculture with defined HLA-E peptide complexes, phenotyping, and ADCC/IFN-γ functional assays

    PMID:30134159

    Open questions at the time
    • Molecular basis of peptide-specific NKG2C licensing not resolved here
    • In vivo selection dynamics untested
  22. 2019 High

    Identified HLA-E as an immune-evasion signal on senescent cells driven by SASP cytokines and p38 MAPK, inhibiting NK and CD8 clearance via NKG2A.

    Evidence senescence induction in fibroblasts, HLA-E flow cytometry, killing assays, p38 inhibition, and NKG2A blockade

    PMID:31160572

    Open questions at the time
    • Peptide presented by senescent HLA-E not identified
    • In vivo senescent-cell clearance not tested
  23. 2019 High

    Mapped HIV-1 Nef-mediated HLA-E downmodulation to the HLA-E cytoplasmic tail, revealing a virus-driven manipulation of HLA-E surface display.

    Evidence primary HIV-1 infection of CD4+ T cells, single Nef/Vpu expression, and HLA-A2/HLA-E tail-swap chimeras with flow cytometry

    PMID:31375574

    Open questions at the time
    • Trafficking machinery engaged by Nef not defined here
    • Net effect on NK vs T cell recognition in vivo unclear
  24. 2020 Medium

    Showed SARS-CoV-2 spike-derived peptide induces HLA-E surface display and suppresses NK degranulation via NKG2A, an early inhibitory immune-evasion mechanism.

    Evidence spike construct transfection of lung epithelial cells, NK coculture, immunofluorescence, and GATA3 inhibition

    PMID:32859121

    Open questions at the time
    • Single-lab study
    • Transcriptional driver of HLA-E upregulation not positively identified
  25. 2021 High

    Demonstrated HLA-E-restricted, HIV Gag-specific CD8+ T cells can suppress viral replication and that their TCRs are transferable, establishing therapeutic potential for HLA-E-restricted T cells.

    Evidence in vitro T cell priming, TCR transduction into allogeneic CD8+ T cells, and HIV-1 replication suppression assays

    PMID:33766848

    Open questions at the time
    • In vivo efficacy untested
    • Breadth of protective epitopes limited
  26. 2021 High

    Revealed a self/non-self discrimination mechanism in which TCR affinity for HLA-E/self-peptide dictates KIR2D versus NKG2C receptor expression on HLA-E-restricted T cells, regulating their activation via HLA-C.

    Evidence RNA-seq, TCR affinity measurement, KIR2D blocking, and CMV UL40/HLA-E tetramer staining

    PMID:33893172

    Open questions at the time
    • Generality across antigens not established
    • In vivo regulatory consequences untested
  27. 2022 High

    Provided the structural rationale for VL9 versus non-VL9 discrimination, showing pathogen peptides reconfigure the TCR-interacting α2 region and make non-VL9 HLA-E complexes conformationally dynamic.

    Evidence multiple crystal structures, SAXS solution analysis, and mutagenesis of HLA-E-exclusive residues

    PMID:35705051

    Open questions at the time
    • Functional receptor outcomes of dynamic complexes not directly quantified here
    • Limited to selected peptides
  28. 2022 High

    Identified a SARS-CoV-2 Nsp13 peptide that, unlike self-peptides, blocks HLA-E:NKG2A engagement and thereby sensitizes infected cells to NKG2A+ NK attack, defining a peptide-driven activating mechanism.

    Evidence peptide-HLA-E binding, NKG2A blocking, NK activation, and viral replication suppression in lung epithelial cells

    PMID:35235832

    Open questions at the time
    • In vivo relevance during infection not established
    • Structural basis of disrupted NKG2A binding not resolved here
  29. 2023 High

    Systematically defined which classical class I signal peptide variants are functionally processed for CD94/NKG2 engagement, showing surface HLA-E level and receptor recognition can be decoupled and that signal peptides compete for HLA-E.

    Evidence quantitative screen of 16 SP variants for HLA-E stabilization and CD94/NKG2A/C binding with competitive loading and NK assays

    PMID:37264229

    Open questions at the time
    • In vivo consequences of SP competition not measured
    • Did not extend to pathogen peptides
  30. 2023 High

    Defined the distinctive trafficking itinerary of HLA-E—ER retention from limited peptide and cytoplasmic-tail-driven surface internalization into late/recycling endosomes—setting it apart from classical class I.

    Evidence live imaging, FRAP, fractionation, cytoplasmic tail mutants, and trafficking inhibitor studies

    PMID:37140910

    Open questions at the time
    • Endosomal recycling regulators not identified
    • Functional consequence of intracellular pool unresolved
  31. 2023 High

    Established a platelet-RGS18-AKT-GSK3β-CREB pathway driving HLA-E on circulating tumor cells to evade NK surveillance and promote metastasis, identifying a targetable upstream regulator.

    Evidence single-cell transcriptomics, NK killing assays, HLA-E knockdown, NKG2A blockade, and in vivo metastasis models

    PMID:36706761

    Open questions at the time
    • Peptide presented by CTC HLA-E not defined
    • Generalizability across tumor types untested
  32. 2023 High

    Established antigen-specific human NK cell memory mediated by NKG2C recognition of HLA-E peptide complexes, with single-cell cloning proving permanent epitope specificity.

    Evidence single-cell NK cloning, HLA-E tetramers, NKG2C blocking, and patient NK phenotyping for HIV and influenza

    PMID:38064568

    Open questions at the time
    • Mechanism of memory imprinting not defined
    • In vivo protective durability untested
  33. 2023 High

    Used high-throughput yeast display to map a broad HLA-E peptidome capable of inhibitory and activating receptor signalling and trained predictive algorithms, expanding the known functional peptide space.

    Evidence yeast-display peptide library screen with HLA-E/CD94/NKG2x selection, NK functional assays, and machine-learning prediction

    PMID:37558657

    Open questions at the time
    • In vivo presentation of predicted peptides unverified
    • Structural rules underlying activating selection not derived
  34. 2023 High

    Showed HLA-E-restricted CD8+ T cells recognize multiple SARS-CoV-2 peptides and suppress replication, with HLA-E surface levels preserved while classical class I is downregulated during infection—favoring HLA-E-restricted surveillance.

    Evidence T cell clone suppression assays and flow cytometry of HLA class I vs HLA-E in infected airway epithelial cells

    PMID:37390223

    Open questions at the time
    • Mechanism preserving HLA-E during infection not defined
    • In vivo protection untested
  35. 2023 High

    Demonstrated EBV LMP-1 peptides presented by HLA-E act through NKG2A to inhibit NK and CD8 responses, while the high-expressing HLA-E*0103 genotype confers protection via BZLF1-specific HLA-E-restricted CD8 T cells.

    Evidence functional NK/CD8 and viral dissemination assays plus a 1404-patient cohort and peptide-HLA-E binding studies

    PMID:36477802

    Open questions at the time
    • Mechanism linking genotype to protective T cell priming not fully resolved
    • Causality of clinical association limited

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the integrated peptide repertoire, allelic dosage, trafficking regulators, and competing signal peptides combine in vivo to set the balance between inhibitory and activating HLA-E signalling for therapeutic targeting.
  • No in vivo map of which peptides dominate HLA-E presentation in healthy versus diseased tissue
  • Endosomal recycling regulators of HLA-E unidentified
  • Predictive rules distinguishing activating from inhibitory peptides not structurally complete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 3 GO:0005768 endosome 2 GO:0005576 extracellular region 1 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 6 R-HSA-392499 Metabolism of proteins 3
Partners
B2MKLRC1KLRC2KLRD1NEFTAP
Complex memberships
HLA-E/β2-microglobulin/peptide class I complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 HLA-E binds to and is the predominant ligand for the NK cell inhibitory receptor CD94/NKG2A, as well as CD94/NKG2B and CD94/NKG2C. HLA-E tetramers (recombinant HLA-E/β2m refolded with MHC leader-sequence peptide) bound specifically to CD94/NKG2A, NKG2B, and NKG2C on transfectants but not to KIR family receptors. Surface expression of HLA-E was sufficient to protect target cells from lysis by CD94/NKG2A+ NK cell clones. HLA-E tetramer binding assay, NK cell cytotoxicity assay, transfection of receptor-expressing cell lines Nature High 9486650
1998 HLA-E is a major ligand for the NK cell inhibitory receptor CD94/NKG2A. Surface stabilization of HLA-E on .221 transfectants with appropriate HLA class I leader sequence peptides was sufficient to confer protection from CD94/NKG2A+ NK-mediated lysis. Neither the Ig-SF KIR receptors nor ILT2/LIR1 mediated this inhibitory effect. Anti-HLA-E, anti-CD94, or anti-CD94/NKG2A antibodies specifically restored NK lysis, confirming the HLA-E:CD94/NKG2A axis. NK cell cytotoxicity assay, antibody blocking, transfection of HLA class I allotypes into .221 cells, cold-loading of peptides Proceedings of the National Academy of Sciences of the United States of America High 9560253
1998 The peptide-binding groove of HLA-E is highly adapted for specific binding of conserved leader sequence peptides from HLA class Ia molecules and is structurally similar to class Ia MHC molecules but with higher specificity along the entire peptide length, unlike the promiscuous grooves of class Ia molecules. Structural analysis / crystallography (framework review) Immunological reviews Medium 9700506
1988 HLA-E (originally designated HLA-6.2) encodes a protein that associates with β2-microglobulin, establishing it as an expressible MHC class I molecule. It maps between HLA-C and HLA-A on chromosome 6. Gene transfer into class I-null human lymphoblastoid cell line, immunoprecipitation to detect β2m association, deletion mutant mapping Journal of immunology High 3260916
2002 The two HLA-E alleles (HLA-E*0101 with Arg107 and HLA-E*0103 with Gly107) differ in peptide affinity, thermal stability, and cell surface expression levels. Crystal structures of HLA-E(G) complexed with two distinct peptides showed no significant conformational differences in the heavy chain between alleles or peptides, but differences in thermal stability and peptide affinity correlated with differential cell surface levels. Crystal structure determination, thermal stability assay, peptide affinity measurements, cell surface expression quantification The Journal of biological chemistry High 12411439
1999 Cell surface expression of HLA-E in mouse cells strictly requires coexpression of human β2-microglobulin. Soluble empty HLA-E/hβ2m complexes display low thermostability, indicating low-affinity β2m interaction contributes to inefficient peptide loading in the ER. The allelic substitution at position 107 (Gly or Arg) greatly affects intracellular transport and cell surface expression. Transfection of HLA-E ± human β2m into mouse myeloma cells, thermal stability assay, FACS quantification of surface expression European journal of immunology High 10064069
2000 Surface expression of HLA-E requires a functioning TAP molecule to transport HLA class I leader peptides into the ER. Without this peptide supply, HLA-E is unstable and degraded before reaching the cell surface. This mechanism allows NK cells to detect downregulation of classical HLA class I molecules in virally infected or tumor cells. Crystallographic studies and functional analyses described in review (citing original experimental work on TAP dependency) Clinical science Medium 10887053
2000 HLA-E is expressed on trophoblast cell surfaces and is recognized by the vast majority of decidual NK cells via CD94/NKG2 receptors. HLA-E tetramer binding to decidual NK cells is inhibited by anti-CD94 antibody. The functional consequence of this interaction is inhibition of decidual NK cell cytotoxicity. HLA-E tetramer staining of decidual NK cells, anti-CD94 antibody blocking, cytotoxicity assays with polyclonal decidual NK cells, immunostaining of trophoblast European journal of immunology High 10898498
2000 HLA-E transcription is induced by IFN-γ through an upstream STAT1 binding site and is inducible by CIITA through the SXY regulatory module. HLA-E is not inducible by NF-κB or IRF1 due to divergence in its promoter regulatory elements. Promoter analysis, transcriptional reporter assays, cis-acting element mapping Human immunology Medium 11137213
2002 HLA-E can be recognized by the αβ T cell receptor (TCR) on CD8+ T cells independently of CD94/NKG2C. An αβ CD8+CD94/NKG2C+ CTL clone recognized RMA-S/HLA-E cells loaded with specific HLA class I leader sequence peptides and also a peptide derived from EBV BZLF-1 protein. Anti-clonotypic TCR antibody blocked lysis while anti-CD94 did not, and HLA-E tetramers stained K14 cells in a TCR-dependent manner. CTL cytotoxicity assay, antibody blocking with anti-TCR and anti-CD94, HLA-E tetramer staining European journal of immunology High 11920559
2003 HLA-E cell surface expression in tumor cell lines is related to the availability of free β2-microglobulin in the cytoplasm. Tumor cells with downregulation of HLA class Ia heavy chains (leading to excess β2m) show increased HLA-E surface expression. Addition of human β2m to tumor cells expressing HLA-E(G) allele increased HLA-E surface expression. Total loss of HLA class Ia expression (including β2m mutations) abolished HLA-E surface expression. Monoclonal antibody staining (3D12) of tumor cell lines, exogenous β2m addition experiments, analysis of cell lines with defined HLA alterations Immunogenetics Medium 12618909
2005 Inhibitory NKG2A/CD94 and activating NKG2E/CD94 receptors bind HLA-E with indistinguishable affinities, both higher than the activating NKG2C/CD94 receptor. The peptide presented by HLA-E significantly influences binding affinity of all three receptors, while HLA-E allelic differences (position 107) had no effect on receptor binding affinity. Quantitative binding affinity measurements and thermodynamic analysis (surface plasmon resonance or equivalent) for three NKG2x/CD94 receptors with HLA-E/peptide complexes Journal of immunology High 15728498
2005 Stable surface expression of HLA-E on porcine cells requires appropriate peptide loading (HLA class I leader sequence peptides). HLA-E expression on porcine cells protected them from lysis by human NKG2A+ NK clones. An HLA-E single-chain trimer (SCT) fusing β2m, peptide, and HLA-E heavy chain was engineered and demonstrated correct folding and function, inhibiting NK cytotoxicity and IFN-γ secretion. Transfection of porcine cell lines, FACS for surface expression, NK cytotoxicity assay, IFN-γ measurement, engineering of single-chain trimer construct Molecular immunology High 15829309
2007 TNFα, IL-1β, and IFN-γ upregulate cell-surface HLA-E expression on endothelial cells and induce release of soluble HLA-E (sHLA-E). HLA-E upregulation protects IFN-γ-activated endothelial cells from NK-mediated lysis, while sHLA-E protects bystander cells. HLA-E protein expression in normal human non-lymphoid organs is mainly restricted to endothelial cells. In vitro cytokine stimulation of endothelial cells, flow cytometry for surface HLA-E, NK cell cytotoxicity assay, ELISA for sHLA-E Blood High 17179229
2008 Crystal structures of HLA-E complexed with two leader peptides (HLA-Cw*07: VMAPRALLL and HLA-G*01: VMAPRTLFL, both at 2.5 Å resolution) showed that allotypic variations in leader sequences do not cause conformational changes in the HLA-E heavy chain, but subtle changes in peptide conformation within the binding groove profoundly affect recognition by CD94-NKG2 receptors. HLA-Cw*07 peptide (poorly recognized) versus HLA-G*01 peptide (high-affinity ligand) differ in conformation within the groove. X-ray crystallography at 2.5 Å resolution, structural comparison of peptide-HLA-E complexes Journal of molecular biology High 18339401
2011 HLA-E expressed on gynecological tumors inhibits CD8+ T cell (CTL) function via CD94/NKG2A receptor interaction. Up to 50% of intraepithelial CTLs expressed the inhibitory CD94/NKG2A receptor. In ovarian cancer, high HLA-E expression completely neutralized the beneficial effect of high CTL infiltration on overall survival, indicating functional inhibition of CTLs by HLA-E:NKG2A interaction in the tumor microenvironment. Immunohistochemistry on 420 tumor sections, in situ detection of NKG2A+ CTLs, survival analysis linked to HLA-E expression and CTL infiltration Proceedings of the National Academy of Sciences of the United States of America Medium 21670276
2014 HCMV-driven expansion of NKG2C+ NK cells requires CD94/NKG2C:HLA-E axis and IL-12 from CD14+ monocytes. Blockade of CD94/NKG2C on NK cells or silencing of HLA-E in HCMV-infected fibroblasts greatly impaired expansion of NKG2C+ NK cells. IL-12 neutralization substantially reduced CD25 upregulation and NKG2C+ subset expansion. NK-monocyte coculture system, NKG2C blockade antibodies, HLA-E siRNA knockdown in infected fibroblasts, IL-12 neutralization The Journal of clinical investigation High 25384219
2015 HLA-E:NKG2A interaction inhibited degranulation of NKG2A+ NK cell subsets with almost all tested peptides. In contrast, NKG2A-NKG2C+ NK cell responses were enhanced only by a restricted set of peptides, most strongly by the HLA-G leader peptide. The HLA-E:G-peptide complex triggered NKG2C receptor internalization (reduced by bafilomycin, indicating lysosomal pathway involvement). NK cell degranulation assay (CD107a expression), peptide-induced HLA-E surface expression on PBMCs, NKG2C receptor internalization assay with bafilomycin Human immunology Medium 26382247
2015 During monocyte-to-macrophage differentiation, newly synthesized HLA-E molecules are primarily trafficked to intracellular autophagy-lysosomal vesicles (colocalizing with LC3 and LAMP1) rather than the cell surface, unlike classical HLA class I. Only a small fraction of HLA-E reaches the cell surface, and NK lysis is still inhibited by anti-NKG2A antibody comparably in differentiated and undifferentiated cells. Confocal microscopy with LC3 and LAMP1 co-localization, subcellular fractionation, flow cytometry, NK cytotoxicity assay in monocytic cell lines and primary monocytes Journal of leukocyte biology Medium 26310830
2018 Crystal structures of HLA-E bound to HIV- and Mtb-derived pathogen peptides reveal that despite preferences for canonical primary anchor residues, HLA-E-bound pathogen peptides can adopt alternative conformations within the peptide-binding groove. Combined structural and mutagenesis analyses show greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. X-ray crystallography of HLA-E/peptide complexes, mutagenesis of binding pockets, biochemical peptide binding studies Nature communications High 30087334
2018 Adaptive NK cells recognize differences between HLA-E-peptide complexes with exquisite specificity via the activating CD94/NKG2C receptor. Prolonged exposure to HLA-E presenting the HLA-G leader peptide VMAPRTLFL enriched adaptive NK cells with low FcεRγ expression, upregulated CD25, increased proliferation, and elevated antibody-dependent cellular cytotoxicity and IFN-γ responses compared to other HLA-E peptide complexes. NK cell coculture with defined HLA-E peptide complexes, flow cytometry for phenotype markers, functional assays for ADCC and IFN-γ, CD25/FcεRγ expression analysis Cell reports High 30134159
2017 HLA-E presents glycopeptides from the Mycobacterium tuberculosis protein MPT32 to CD8+ T cells. Recognition by an HLA-E-restricted CD8+ T cell clone required N-terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by Rv1002c, establishing the first post-translationally modified Mtb antigen presented by HLA-E. T cell clone cytotoxicity/recognition assay, HLA-E tetramer staining, Rv1002c mannosyltransferase mutant bacteria, glycopeptide synthesis Scientific reports Medium 28676677
2019 Senescent dermal fibroblasts upregulate HLA-E expression, and this HLA-E interacts with the inhibitory receptor NKG2A on NK cells and highly differentiated CD8+ T cells to inhibit immune responses against senescent cells. HLA-E induction in senescent cells is driven by SASP-related pro-inflammatory cytokines and regulated by p38 MAP kinase signaling in vitro. Blocking HLA-E:NKG2A interaction boosted immune responses against senescent cells in vitro. Senescence induction in primary fibroblasts, flow cytometry for HLA-E expression, NK/CD8 T cell killing assay, p38 inhibitor treatment, NKG2A blocking antibody Nature communications High 31160572
2019 HIV-1 Nef protein downmodulates HLA-E surface levels on infected primary CD4+ T cells by targeting the cytoplasmic tail of HLA-E. Tail-swap experiments exchanging the cytoplasmic tail of HLA-A2 with that of HLA-E demonstrated Nef specifically targets the HLA-E cytoplasmic tail. HIV-1 mutants lacking functional Nef (and to a lesser extent Vpu) showed impaired HLA-E downmodulation. Primary HIV-1 strain infection of CD4+ T cells, single Nef/Vpu expression in T cell lines, cytoplasmic tail swap constructs (HLA-A2/HLA-E chimeras), flow cytometry Journal of virology High 31375574
2020 SARS-CoV-2 spike 1 protein (SP1) expressed intracellularly in lung epithelial cells induces HLA-E surface expression via presentation of an SP1-derived HLA-E-binding peptide, leading to increased NKG2A/CD94 expression on NK cells and reduced NK cell degranulation via HLA-E/NKG2A interaction. The GATA3 transcription factor was ruled out as responsible for HLA-E upregulation. Transfection of lung epithelial cells with SARS-CoV-2 spike constructs, flow cytometry for HLA-E and NK cell activation markers, NK cell co-culture assay, immunofluorescence, GATA3 inhibitor experiments Cells Medium 32859121
2021 HLA-E-restricted HIV-1-specific CD8+ T cell clones and allogeneic CD8+ T cells transduced with their TCRs suppressed HIV-1 replication in CD4+ T cells in vitro. HLA-E-restricted T cells were primed in vitro and recognized Gag-derived peptides presented by HLA-E. In vitro T cell priming, TCR transduction into allogeneic CD8+ T cells, HIV-1 replication suppression assay in CD4+ T cells Science immunology High 33766848
2022 The SARS-CoV-2 Non-structural protein 13 (Nsp13) encodes a peptide presented by HLA-E that prevents binding of HLA-E to the inhibitory receptor NKG2A (unlike self-peptides), rendering target cells susceptible to NKG2A-expressing NK cell attack. NKG2A+ NK cells were specifically activated and proficiently limited SARS-CoV-2 replication in infected lung epithelial cells in vitro. Peptide-HLA-E binding assay, NKG2A blocking experiments, NK cell activation assay, viral replication suppression assay in lung epithelial cells, patient NK cell phenotyping Cell reports High 35235832
2022 Crystal structures of HLA-E bound to VL9 (MHC class Ia signal peptides) versus pathogen-derived peptides reveal that VL9 positions close to the α2 helix via three HLA-E-exclusive amino acids. Non-VL9 pathogen peptides introduce an alternative peptide-binding motif and re-configure a key TCR-interacting α2 region, providing the structural basis for VL9- versus non-VL9-HLA-E immune discrimination. Small-angle X-ray scattering revealed that non-VL9 HLA-E complexes are conformationally dynamic in solution compared to VL9 complexes. X-ray crystallography of multiple HLA-E/peptide complexes, small-angle X-ray scattering (SAXS), mutagenesis of key residues, peptide excess experiments Cell reports High 35705051
2023 Among 16 common classical HLA class I signal peptide variants, only 6 can be efficiently processed to generate epitopes enabling CD94/NKG2 engagement ('functional SPs'). The single functional HLA-B SP (HLA-B/-21M) induces high HLA-E expression but provides the lowest NKG2 receptor recognition, and competes with other SPs for providing epitope to HLA-E, thereby reducing overall CD94/NKG2A recognition of target cells. Systematic quantitative analysis of 16 SP variants for HLA-E stabilization and CD94/NKG2A/C binding, competitive peptide loading assays, NK cell functional assays Nature immunology High 37264229
2023 HLA-E is largely retained in the endoplasmic reticulum after synthesis due to limited supply of high-affinity peptides, with further fine-tuning by its cytoplasmic tail. Once at the cell surface, HLA-E is unstable and rapidly internalized; its cytoplasmic tail is required for HLA-E internalization, resulting in enrichment in late and recycling endosomes. This distinguishes HLA-E trafficking from classical HLA class I. Live cell imaging, FRAP, subcellular fractionation, cytoplasmic tail deletion/mutation constructs, trafficking inhibitor studies, comparison with classical HLA class I The Journal of experimental medicine High 37140910
2023 HLA-E presents EBV LMP-1-derived peptides (GGDPHLPTL or GGDPPLPTL) to NKG2A+ NK and CD8+ T cells in an inhibitory manner. EBV strains encoding both peptide variants were associated with symptomatic EBV reactivations. The highly expressed HLA-E*0103/0103 genotype is protective against infectious mononucleosis through induction of BZLF1-specific HLA-E-restricted CD8+ T cell responses that efficiently prevent viral dissemination in vitro. Functional NK and CD8+ T cell assays, viral dissemination assay in vitro, large cohort study (1404 patients), peptide-HLA-E binding experiments Blood High 36477802
2023 Platelet-derived RGS18 promotes HLA-E expression on circulating tumor cells (CTCs) through the AKT-GSK3β-CREB signaling pathway, enabling CTCs to evade NK cell-mediated immune surveillance via the HLA-E:CD94-NKG2A immune checkpoint. Disruption of this interaction by NKG2A blockade or HLA-E knockdown enhanced NK-mediated killing in vitro and prevented tumor metastasis in vivo. Single-cell transcriptomics, in vitro NK killing assay, in vivo tumor metastasis mouse model, HLA-E knockdown, NKG2A blockade, RGS18 overexpression/knockdown with AKT/GSK3β/CREB pathway analysis Cancer cell High 36706761
2023 Antigen-specific human NK cell memory against HIV and influenza is mediated largely through the activating CD94/NKG2C receptor recognizing HLA-E in an epitope-specific manner. Single-cell cloning validated permanent antigen specificity of individual memory NK cells. KLRG1, α4β7, and NKG2C were identified as biomarkers of antigen-specific NK memory, and individual HLA-E-restricted peptides from HIV-1 and influenza constitute dominant NK cell responses in infected persons. Single-cell cloning of NK cells, HLA-E tetramer staining, NKG2C blocking, peptide-HLA-E binding assays, immunophenotyping of infected patient NK cells Science immunology High 38064568
2023 High-throughput yeast-display screening identified 500 unique peptides that bind both HLA-E and CD94/NKG2A or CD94/NKG2C, including CMV proteome-derived peptides. Peptides selectively activating NKG2C+ NK cells were identified. Prediction algorithms trained on yeast-display selections identified human and CMV proteome-derived HLA-E-presented peptides capable of signaling through both inhibitory and activating receptors. Yeast-displayed peptide library screen, HLA-E/CD94/NKG2x binding selection, NK cell functional assays, machine learning-based prediction algorithm Nature communications High 37558657
2021 HLA-E-restricted CD8+ T cells from CMV-infected individuals express inhibitory KIR2DL1 and KIR2DL2/L3 when bearing high-affinity TCRs for HLA-E/self-peptide, while T cells with lower-affinity TCRs expressed the activating receptor NKG2C. Activation of high-affinity TCR-bearing T cells was regulated by KIR2D receptor interaction with HLA-C, providing a mechanism for self/non-self discrimination by HLA-E-restricted T cells. RNA sequencing, flow cytometry, TCR affinity measurement, KIR2D blocking experiments, CMV UL40/HLA-E tetramer staining Science immunology High 33893172
2023 HLA-E-restricted SARS-CoV-2-specific CD8+ T cell clones with diverse TCRs recognized five SARS-CoV-2-derived peptides presented by HLA-E and suppressed viral replication in Calu-3 lung epithelial cells. SARS-CoV-2 infection markedly downregulated classical HLA class I (HLA-A, B, C) expression while HLA-E expression was not affected, enabling continued HLA-E-restricted T cell recognition. T cell clone isolation and characterization, HLA-E peptide-specific suppression of SARS-CoV-2 replication, flow cytometry for HLA class I and HLA-E surface expression in infected cells, primary reconstituted human airway epithelial cells Science immunology High 37390223

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1823 9486650
1998 HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proceedings of the National Academy of Sciences of the United States of America 844 9560253
2017 HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells. Nature biotechnology 490 28504668
2019 Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nature communications 430 31160572
2000 HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. European journal of immunology 290 10898498
2023 Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance. Cancer cell 272 36706761
2002 HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities. The Journal of biological chemistry 268 12411439
1990 Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. Human immunology 225 2249951
1988 HLA-E. A novel HLA class I gene expressed in resting T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 217 3260916
2011 HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8⁺ T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 190 21670276
2020 The NKG2A-HLA-E Axis as a Novel Checkpoint in the Tumor Microenvironment. Clinical cancer research : an official journal of the American Association for Cancer Research 187 32409305
2005 Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics. Journal of immunology (Baltimore, Md. : 1950) 176 15728498
2007 Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation. Blood 161 17179229
2014 IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion. The Journal of clinical investigation 159 25384219
1998 Structure and function of the human MHC class Ib molecules HLA-E, HLA-F and HLA-G. Immunological reviews 142 9700506
2003 Analysis of HLA-E expression in human tumors. Immunogenetics 136 12618909
2000 Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G. Human immunology 115 11137213
2008 The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity. Tissue antigens 106 18946929
1992 Polymorphism at the HLA-E locus predates most HLA-A and -B polymorphism. Human immunology 106 1618657
2022 NKG2A and HLA-E define an alternative immune checkpoint axis in bladder cancer. Cancer cell 104 36099881
2002 Human T cell receptor-mediated recognition of HLA-E. European journal of immunology 90 11920559
2008 Subtle changes in peptide conformation profoundly affect recognition of the non-classical MHC class I molecule HLA-E by the CD94-NKG2 natural killer cell receptors. Journal of molecular biology 88 18339401
2020 SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway. Cells 87 32859121
2011 Clinical significance of the HLA-E and CD94/NKG2 interaction. Archivum immunologiae et therapiae experimentalis 81 21800130
2010 The emerging role of HLA-E-restricted CD8+ T lymphocytes in the adaptive immune response to pathogens and tumors. Journal of biomedicine & biotechnology 81 20634877
2019 Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8+ Tumor-Infiltrating T Lymphocyte Responses. Cancer immunology research 80 31213473
2018 Distinct HLA-E Peptide Complexes Modify Antibody-Driven Effector Functions of Adaptive NK Cells. Cell reports 77 30134159
2016 Characteristics of HLA-E Restricted T-Cell Responses and Their Role in Infectious Diseases. Journal of immunology research 75 27699181
2018 Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding. Nature communications 73 30087334
1999 Cell surface expression of HLA-E: interaction with human beta2-microglobulin and allelic differences. European journal of immunology 73 10064069
2006 The involvement of HLA-E and -F in pregnancy. Journal of reproductive immunology 71 16487601
2016 HLA-E expression and its clinical relevance in human renal cell carcinoma. Oncotarget 61 27589686
2014 Clinical and immunological significance of HLA-E in stem cell transplantation and cancer. Tissue antigens 58 25413103
2023 HLA class I signal peptide polymorphism determines the level of CD94/NKG2-HLA-E-mediated regulation of effector cell responses. Nature immunology 57 37264229
2007 HLA-E*0101 and HLA-G*010101 reduce the risk of Behcet's disease. Tissue antigens 57 17257316
2005 HLA-E expression on porcine cells: protection from human NK cytotoxicity depends on peptide loading. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 57 16095487
2023 Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis. Science immunology 54 38064568
2015 HLA-E regulates NKG2C+ natural killer cell function through presentation of a restricted peptide repertoire. Human immunology 54 26382247
2022 SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells. Cell reports 53 35235832
2022 Disruption of the NKG2A:HLA-E Immune Checkpoint Axis to Enhance NK Cell Activation against Cancer. Vaccines 53 36560403
2021 HLA-E-restricted, Gag-specific CD8+ T cells can suppress HIV-1 infection, offering vaccine opportunities. Science immunology 53 33766848
2019 Dimorphism of HLA-E and its Disease Association. International journal of molecular sciences 49 31690066
2020 The unconventional role of HLA-E: The road less traveled. Molecular immunology 48 32113130
2007 Immune-refractory cancers and their little helpers--an extended role for immunetolerogenic MHC molecules HLA-G and HLA-E? Seminars in cancer biology 47 17768067
2006 HLA-E and immunobiology of pregnancy. Tissue antigens 47 16573557
2012 HLA-E expression in cervical adenocarcinomas: association with improved long-term survival. Journal of translational medicine 46 22947189
2009 Clinical significance of HLA-E*0103 homozygosity on survival after allogeneic hematopoietic stem-cell transplantation. Transplantation 45 19696636
2015 Human leukocyte antigen (HLA)-E and HLA-F expression in gastric cancer. Anticancer research 44 25862890
2005 An HLA-E single chain trimer inhibits human NK cell reactivity towards porcine cells. Molecular immunology 43 15829309
2009 HLA-E and HLA-E-bound peptides: recognition by subsets of NK and T cells. Current pharmaceutical design 42 19860683
2024 Unlocking the therapeutic potential of the NKG2A-HLA-E immune checkpoint pathway in T cells and NK cells for cancer immunotherapy. Journal for immunotherapy of cancer 37 39486805
2023 HLA-E-restricted immune responses are crucial for the control of EBV infections and the prevention of PTLD. Blood 37 36477802
2023 Intracellular trafficking of HLA-E and its regulation. The Journal of experimental medicine 37 37140910
2022 Simultaneous editing of TCR, HLA-I/II and HLA-E resulted in enhanced universal CAR-T resistance to allo-rejection. Frontiers in immunology 37 36532006
2018 HLA-E Peptide Repertoire and Dimorphism-Centerpieces in the Adaptive NK Cell Puzzle? Frontiers in immunology 37 30386347
2017 HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. Scientific reports 37 28676677
2016 HLA-E allelic genotype correlates with HLA-E plasma levels and predicts early progression in chronic lymphocytic leukemia. Cancer 37 27859015
2023 KLRC1 knockout overcomes HLA-E-mediated inhibition and improves NK cell antitumor activity against solid tumors. Frontiers in immunology 35 37675109
2019 HLA-E: exploiting pathogen-host interactions for vaccine development. Clinical and experimental immunology 35 30968409
2019 Primary HIV-1 Strains Use Nef To Downmodulate HLA-E Surface Expression. Journal of virology 35 31375574
2010 HLA-G and HLA-E in patients with juvenile idiopathic arthritis. Rheumatology (Oxford, England) 35 21186170
2020 Detailed and atypical HLA-E peptide binding motifs revealed by a novel peptide exchange binding assay. European journal of immunology 33 32716529
2020 Human Amnion Epithelial Cells Impair T Cell Proliferation: The Role of HLA-G and HLA-E Molecules. Cells 33 32961693
2018 Identification of novel HIV-1-derived HLA-E-binding peptides. Immunology letters 33 30172717
2014 HLA-E: a novel player for histocompatibility. Journal of immunology research 33 25401109
2023 High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation. Nature communications 31 37558657
2022 NKG2A-checkpoint inhibition and its blockade critically depends on peptides presented by its ligand HLA-E. Immunology 31 35596615
2015 Regulation and trafficking of the HLA-E molecules during monocyte-macrophage differentiation. Journal of leukocyte biology 31 26310830
2017 New insights in HLA-E polymorphism by refined analysis of the full-length gene. HLA 29 28127896
2007 Play it in E or G: utilization of HLA-E and -G in xenotransplantation. Xenotransplantation 29 17489859
2021 HLA-E-restricted HIV-1-specific CD8+ T cell responses in natural infection. The Journal of clinical investigation 28 34228645
2019 Enhancing Natural Killer and CD8+ T Cell-Mediated Anticancer Cytotoxicity and Proliferation of CD8+ T Cells with HLA-E Monospecific Monoclonal Antibodies. Monoclonal antibodies in immunodiagnosis and immunotherapy 26 31009335
2016 Expression of MHC class I-related molecules MICA, HLA-E and EPCR shape endothelial cells with unique functions in innate and adaptive immunity. Human immunology 26 26916837
2009 HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia. Arthritis research & therapy 26 19912639
1997 Description of a new HLA-E (E*01031) allele and its frequency in the Spanish population. Human immunology 26 9154460
2022 Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity. Communications biology 24 35347236
2012 Increased HLA-E expression in white matter lesions in multiple sclerosis. Immunology 24 23039207
2023 Co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells attenuates human NK cell-mediated degranulation. Frontiers in immunology 23 37529053
2022 Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes. Cell reports 23 35705051
2020 HLA-E expression in diffuse glioma: relationship with clinicopathological features and patient survival. BMC neurology 23 32066399
2016 Evaluation of HLA-G, HLA-E, and PD-L1 proteins in oral osteosarcomas. Oral surgery, oral medicine, oral pathology and oral radiology 23 28159587
2012 HLA-E polymorphisms in hematopoietic stem cell transplantation. Tissue antigens 23 22256791
2022 HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation. Cancer genomics & proteomics 22 35181585
2021 Natural killer cell receptors regulate responses of HLA-E-restricted T cells. Science immunology 22 33893172
1999 Detection of HLA-E and -G DNA alleles for population and disease studies. Cellular and molecular life sciences : CMLS 22 11212362
2000 Molecular basis of human natural killer cell recognition of HLA-E (human leucocyte antigen-E) and its relevance to clearance of pathogen-infected and tumour cells. Clinical science (London, England : 1979) 21 10887053
2025 HLA-E: Immune Receptor Functional Mechanisms Revealed by Structural Studies. Immunological reviews 20 39753525
2023 HLA-E-restricted SARS-CoV-2-specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation. Science immunology 20 37390223
2023 XPO1 inhibition sensitises CLL cells to NK cell mediated cytotoxicity and overcomes HLA-E expression. Leukemia 20 37528310
2020 HLA-E-restricted CD8+ T Lymphocytes Efficiently Control Mycobacterium tuberculosis and HIV-1 Coinfection. American journal of respiratory cell and molecular biology 20 31697586
2019 Capturing the antigen landscape: HLA-E, CD1 and MR1. Current opinion in immunology 20 31445404
2018 Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma. Human immunology 20 29499226
2016 Involvement of IL-10 and TGF-β in HLA-E-mediated neuroblastoma migration and invasion. Oncotarget 20 27322426
2021 HLA-G and HLA-E Immune Checkpoints Are Widely Expressed in Ewing Sarcoma but Have Limited Functional Impact on the Effector Functions of Antigen-Specific CAR T Cells. Cancers 19 34201079
2016 HLA-E polymorphism and soluble HLA-E plasma levels in chronic hepatitis B patients. HLA 19 26956431
2015 Relevance of HLA-G, HLA-E and IL-10 expression in lip carcinogenesis. Human immunology 19 26723902
2024 CD8+ T cell targeting of tumor antigens presented by HLA-E. Science advances 18 38728394
2017 HLA-E regulatory and coding region variability and haplotypes in a Brazilian population sample. Molecular immunology 18 28946074
2013 HLA-E restricted CD8+ T cell subsets are phenotypically altered in multiple sclerosis patients. Multiple sclerosis (Houndmills, Basingstoke, England) 18 24144875
2024 Targeting HLA-E-overexpressing cancers with a NKG2A/C switch receptor. Med (New York, N.Y.) 17 39423821

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