Affinage

HLA-B

HLA class I histocompatibility antigen, B alpha chain · UniProt P01889

Length
362 aa
Mass
40.5 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-B encodes a highly polymorphic MHC class I heavy chain that assembles with β2-microglobulin and a peptide cargo and traffics to the cell surface to present antigens to CD8+ T cells and NK cells (PMID:63373, PMID:93026). The heavy chain is inserted asymmetrically into the rough ER as a type I transmembrane glycoprotein with its extracellular domain facing the lumen, and β2-microglobulin association — not glycosylation — is the prerequisite for conformational maturation, oligosaccharide processing, and ER-to-surface transport (PMID:356051, PMID:93026, PMID:7000762). Allelic polymorphism governs nearly every functional property of the molecule: residues near the C-terminal end of the peptide-binding groove set tapasin dependence and the stability of peptide-deficient forms (PMID:24790147), while a subset of allotypes achieve TAP-independent assembly through high peptide-loading efficiency and high intrinsic stability of the empty heterodimer (PMID:29995954). Polymorphisms also dictate the peptide-binding motif and peptidome breadth, intracellular maturation rate, and surface expression in an allele- and cell-type-dependent manner (PMID:9331948, PMID:19838694, PMID:29989547). The Bw4/Bw6 supertypic epitopes encoded by residues 74–83 of the α1 domain (PMID:2777338) determine recognition by the NK-cell receptors KIR3DL1 and KIR3DS1, where the combination of receptor allotype/density and HLA-B Bw4 subtype calibrates NK education and effector function — a combinatorial logic with consequences for HIV/AIDS progression and post-transplant AML outcomes (PMID:8046332, PMID:12134147, PMID:17496894, PMID:26962229, PMID:28520526). Such NK recognition is peptide-dependent, as shown for KIR3DS1 engagement of HLA-B*57:01 and KIR2DL3 recognition of the C1-bearing HLA-B*46:01 (PMID:25740999, PMID:28514659). HLA-B is also a determinant of viral immune evasion, resisting HIV-1 Nef downregulation and HCMV US11-mediated ERAD relative to HLA-A (PMID:26787826, PMID:31527904). Finally, specific allotypes mediate drug-hypersensitivity reactions through direct, processing-independent drug binding within the peptide-binding groove or covalent haptenation of bound peptides, as established for carbamazepine on HLA-B*1502 and abacavir/flucloxacillin on HLA-B*57:01 (PMID:22322005, PMID:29782330, PMID:33633747), and HLA-B*27 subtypes present self and microbial peptides to autoreactive public TCRs in spondyloarthritis (PMID:36477533).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1976 High

    Established that HLA-B private specificities and the public Bw4/Bw6 antigens are distinct epitopes carried on a single polypeptide, defining the molecular target as one heavy chain rather than separate molecules.

    Evidence Sequential immunoprecipitation with alloantisera on radiolabeled, papain-solubilized lymphoblastoid membranes

    PMID:63373

    Open questions at the time
    • Did not define the amino acid residues encoding the epitopes
    • No structural model of the heavy chain
  2. 1980 High

    Defined the biosynthetic and topological logic of the molecule — type I transmembrane insertion into the ER with β2m association as the obligatory step for maturation and surface transport — answering how the heavy chain becomes a functional surface glycoprotein.

    Evidence Lipid vesicle reconstitution with protease topology mapping; pulse-chase labeling with glycosylation inhibition and β2m-deficient Daudi cells

    PMID:356051 PMID:7000762 PMID:93026

    Open questions at the time
    • Did not identify the chaperone machinery (tapasin/TAP) controlling peptide loading
    • Allele-specific differences in maturation not addressed
  3. 1989 High

    Mapped the Bw4/Bw6 supertypic specificities to residues 74–83 of the α1 helix, providing the structural basis later linking HLA-B polymorphism to NK receptor recognition.

    Evidence Allele cloning, nucleotide sequencing, and monoclonal antibody epitope mapping

    PMID:2777338

    Open questions at the time
    • No receptor for these epitopes yet identified
    • Functional consequence of the epitope not established
  4. 1997 High

    Showed that HLA-B allotypes carry defined peptide-binding motifs and that an α3-domain residue (Thr245) tunes CD8 co-receptor binding, linking polymorphism to both peptide selection and CD8 engagement.

    Evidence Transfection, pool peptide sequencing, in vitro CD8 binding, and T245A site-directed mutagenesis

    PMID:9331948

    Open questions at the time
    • CD8-binding effect characterized for a single allotype
    • Physiological consequence of weak CD8 binding incompletely resolved
  5. 1994 High

    Identified HLA-B as the specific ligand for the NK receptor KIR3DL1, establishing HLA-B's role in NK cell recognition beyond T cell antigen presentation.

    Evidence NK clonal cytotoxicity, HLA-allele transfection, and DX9 mAb blocking

    PMID:8046332

    Open questions at the time
    • Did not define which residues confer KIR3DL1 specificity
    • Peptide-dependence of recognition not addressed
  6. 2008 High

    Demonstrated that KIR3DL1/KIR3DS1 allotypes act epistatically with HLA-B Bw4 subtypes to modulate HIV/AIDS progression in a density- and binding-strength-dependent hierarchy, translating the molecular ligand relationship into in vivo immune control.

    Evidence Large-cohort genetic epistasis association studies of KIR and HLA-B subtypes in HIV-infected individuals

    PMID:12134147 PMID:17496894

    Open questions at the time
    • Genetic association does not establish the molecular mechanism of NK activation at the cellular level
    • Causal peptide contribution not yet tested
  7. 2009 High

    Showed that a single residue (position 116) controls peptide-loading efficiency, TAP binding, and maturation rate, linking fine allelic variation to trafficking kinetics and AIDS progression rate.

    Evidence Pulse-chase, TAP co-IP, peptide-binding and thermostability assays comparing HLA-B*3501 vs *3503

    PMID:19838694

    Open questions at the time
    • Single allele pair from a single lab
    • Direct in vivo link between trafficking kinetics and clinical outcome not proven
  8. 2014 High

    Systematically defined polymorphic determinants of tapasin dependence and empty-form stability across 27 alleles, explaining why HLA-B allotypes differ in their assembly requirements.

    Evidence In vitro refolding, aggregation, and tapasin-deficient cell expression across 27 HLA-B alleles

    PMID:24790147

    Open questions at the time
    • Single lab
    • Precise structural mechanism of residue effects on tapasin engagement not crystallographically defined
  9. 2018 High

    Established TAP-independent assembly as a property of a subset of allotypes and connected it to resistance to viral TAP inhibitors, and revealed allele/cell-type-dependent surface expression and a non-canonical adhesion-amplifying role for empty HLA-B conformers.

    Evidence Expression of 27 alleles in TAP-deficient cells, peptide-binding and NK assays; primary-cell flow cytometry; tetramer/synapse imaging of empty HLA-B*35:01

    PMID:29741477 PMID:29989547 PMID:29995954

    Open questions at the time
    • Generality of empty-conformer adhesion role across allotypes unknown
    • In vivo relevance of TAP-independence to infection control not directly demonstrated
  10. 2017 Medium

    Demonstrated peptide-dependence of NK recognition for HLA-B, including KIR3DS1 engagement of HLA-B*57:01 and KIR2DL3 recognition of a C1-epitope HLA-B*46:01 generated by intergenic mini-conversion, refining the rules of NK ligand formation.

    Evidence Defined-peptide KIR binding/NK functional assays; high-resolution immunopeptidomics with KIR2DL3 binding of peptide subsets

    PMID:25740999 PMID:28514659

    Open questions at the time
    • No crystal structures of these peptide-KIR complexes reported
    • Quantitative contribution of peptide identity to NK activation in vivo unresolved
  11. 2016 High

    Defined HLA-B as a relatively resistant target of viral immune evasion, with locus-specific resistance to HIV-1 Nef downregulation and HCMV US11-mediated ERAD, mapping the viral and host sequence determinants of differential targeting.

    Evidence Nef clone panel with site-directed mutagenesis and T cell recognition assays; US11 domain mutagenesis with peptidomics and co-IP

    PMID:26787826 PMID:31527904

    Open questions at the time
    • Structural basis of HLA-B resistance to US11/Nef not fully resolved
    • Whether resistance generalizes across all HLA-B allotypes untested
  12. 2012 High

    Established that HLA-B mediates drug hypersensitivity through direct, metabolism-independent drug binding within the peptide-binding groove and through peptide haptenation, identifying causal residues and demonstrating CD8+ T cell activation.

    Evidence SPR drug-HLA binding, mutagenesis, and CTL assays (carbamazepine/HLA-B*1502); transgenic mouse and immunopeptidomics (abacavir/flucloxacillin, HLA-B*57:01)

    PMID:22322005 PMID:29782330 PMID:33633747

    Open questions at the time
    • Why specific allotypes confer hypersensitivity to specific drugs not fully predictable
    • Role of CD4 help/costimulation thresholds in clinical reactions incompletely defined
  13. 2022 High

    Provided the structural and immunological basis for HLA-B*27-restricted autoimmunity, showing public BV9 TCRs cross-react with self and microbial peptides presented by HLA-B*27:05, and that disease-associated B*27 subtypes show elevated conformational dynamics.

    Evidence TCR isolation, yeast-display peptide libraries, peptide-MHC-TCR structures; crystallography with isotope-edited IR spectroscopy across B*27 subtypes; B27 immunopeptidomics

    PMID:20112406 PMID:26748477 PMID:36477533

    Open questions at the time
    • Causal chain from molecular mimicry/dynamics to clinical disease not fully established
    • No functional T cell validation in the immunopeptidomics dataset
  14. 2020 Medium

    Implicated HLA-B in cancer-cell-intrinsic processes — cytokine-driven immunopeptidome remodeling, preferential sorting into extracellular vesicles, and modulation of ITGB1/migration — suggesting roles beyond classical antigen presentation.

    Evidence Immunopeptidomics under cytokine stimulation and in extracellular vesicles; HLA-B siRNA knockdown with migration and ITGB1 readouts in pancreatic cancer lines

    PMID:30833945 PMID:32194036 PMID:34211107

    Open questions at the time
    • Migration effect is cell-line-dependent and mechanistically unclear
    • Single-lab/single-cell-line observations not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HLA-B nanoscale surface organization, allele-specific clustering, and the balance of canonical versus non-canonical (empty-conformer, vesicle-sorted) presentation integrate to set the threshold for T cell and NK cell activation remains unresolved.
  • No unifying model linking surface clustering to functional output
  • Allotype-by-cell-type rules for non-canonical presentation incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 5 GO:0005198 structural molecule activity 3 GO:0048018 receptor ligand activity 3
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-1643685 Disease 5 R-HSA-392499 Metabolism of proteins 4
Partners
B2MCD8KIR2DL3KIR3DL1KIR3DS1TAP1TAP2TAPASIN
Complex memberships
MHC class I peptide-loading complex (heavy chain/β2-microglobulin/peptide)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1976 HLA-B specificities and the public antigens Bw4/Bw6 are distinct antigenic determinants located on the same polypeptide chain. Sequential immunoprecipitation experiments demonstrated that HLA-B7 and Bw6, which are genetically associated, are different epitopes on the same molecule, as are HLA-B12 and Bw4. Sequential immunoprecipitation with alloantisera on 125I-labeled, papain-solubilized lymphoblastoid cell membrane preparations European journal of immunology High 63373
1978 Purified HLA-A and HLA-B molecules can be reconstituted into phospholipid vesicles with asymmetric orientation (COOH-terminus anchored in membrane, extracellular domain facing outward), and remain antigenically active in this state. Protease cleavage confirmed the membrane topology consistent with a type I transmembrane protein. Detergent solubilization, lipid vesicle reconstitution, protease cleavage, anti-β2-microglobulin binding, and complement-mediated cytotoxicity inhibition assays Proceedings of the National Academy of Sciences of the United States of America High 356051
1979 HLA-A and HLA-B heavy chains are synthesized with high-mannose oligosaccharides, associate with β2-microglobulin within the first 10–15 min after synthesis in the ER, undergo oligosaccharide processing to complex form ~30 min post-synthesis, and appear at the cell surface 60–80 min post-synthesis. β2-microglobulin association precedes and is required for conformational maturation. Pulse-chase metabolic labeling, immunoprecipitation with conformation-sensitive antisera, oligosaccharide processing analysis in human B-lymphoblastoid cells Cell High 93026
1980 HLA-A and HLA-B heavy chains are inserted asymmetrically into the rough ER as transmembrane polypeptides; β2-microglobulin association is necessary for subsequent oligosaccharide processing and intracellular transport to the cell surface, whereas glycosylation itself is not required for asymmetric insertion, transport, or surface expression. Pulse-chase biosynthetic labeling, subcellular fractionation, glycosylation inhibition (tunicamycin), and Daudi (β2m-deficient) cell line analysis The Journal of biological chemistry High 7000762
1989 The Bw4 and Bw6 supertypic specificities of HLA-B are encoded by residues 74–83 in the α-helical region of the α1 domain. Bw6 is distinguished by Ser at position 77 and Asn at position 80; Bw4 is characterized by at least seven different amino acid exchange patterns at positions 77 and 80–83. Gene cloning, nucleotide sequencing of HLA-B38 and B39 alleles, sequence comparison, and monoclonal antibody reactivity mapping Immunogenetics High 2777338
1994 NKB1 (KIR3DL1), a 70-kD glycoprotein expressed on a subset of NK cells, is a receptor that specifically recognizes certain HLA-B alleles (e.g., HLA-B*5101, HLA-B*5801) but not HLA-A or HLA-C alleles. Anti-NKB1 mAb DX9 inhibits NK-cell lysis of target cells transfected with those specific HLA-B alleles. NK cell clonal assays, HLA-class-I-deficient cell transfection, mAb blocking experiments with DX9, flow cytometry The Journal of experimental medicine High 8046332
1997 HLA-B*4801 binds nonamer peptides with Gln or Lys at position 2 and Leu at the C-terminus (peptide-binding motif). The allotype binds CD8α homodimers weakly due to Thr245 in the α3 domain; mutating Thr245→Ala restores CD8 binding to levels comparable to other HLA-I allotypes. Despite low CD8 affinity, alloreactive T cells recognizing B*4801 are still inhibited by anti-CD8 mAbs. Transfection into HLA-class-I-deficient 221 cells, pool sequence analysis of endogenous peptides, in vitro cell-cell CD8 binding assay, site-directed mutagenesis (T245A), flow cytometry Tissue antigens High 9331948
2002 The activating NK receptor KIR3DS1, in epistatic combination with HLA-B alleles encoding Bw4-80Ile, delays progression to AIDS after HIV-1 infection. Neither locus alone conferred the protective effect; the strongest synergistic effect was on CD4+ T-cell depletion, consistent with KIR3DS1-mediated NK-cell activity triggered by HLA-B Bw4-80Ile ligands. Genetic epistasis analysis in >1,000 HIV-infected individuals; population-based association study with KIR and HLA typing Nature genetics High 12134147
2007 KIR3DL1 allotypes differing in NK cell expression levels and inhibitory capacity combine with HLA-B Bw4 allotypes to produce a hierarchy of effects on AIDS progression and HIV RNA levels. Higher-expression KIR3DL1 allotypes combined with HLA-B Bw4-80Ile provide the greatest protection, correlating with previously defined functional differences between KIR3DL1 allotypes. Large-cohort genetic association study (>1,500 HIV+ individuals) with KIR3DL1/HLA-B subtype genotyping; functional correlation with published NK cell assay data Nature genetics High 17496894
2009 HLA-B*3503 (Phe116) shows reduced intracellular maturation rate and enhanced binding to TAP compared with HLA-B*3501 (Ser116), which differ only at position 116. Both allotypes are relatively tapasin-independent. The reduced peptide loading efficiency of HLA-B*3503 is proposed to account for its slower ER-Golgi trafficking and association with rapid AIDS progression. Pulse-chase labeling, TAP co-immunoprecipitation, in vitro peptide binding assay with peptide libraries, thermostability assay, intracellular trafficking analysis in HIV-infected and uninfected cells Immunogenetics High 19838694
2012 HLA-B*1502, loaded with endogenous peptide, directly binds carbamazepine (CBZ) without intracellular drug metabolism or antigen processing, and this trimolecular HLA-B*1502/peptide/β2m complex activates CBZ-specific cytotoxic T lymphocytes. Three residues (Asn63, Ile95, Leu156) in the peptide-binding groove are critical for CBZ presentation; Asn63 (shared by the B75 family) is the key residue. Structural modifications of the CBZ ring that abolish HLA-B*1502 binding also abolish CTL activation. Surface plasmon resonance, peptide-binding assay, site-directed mutagenesis of HLA-B*1502, CTL activation assays, computer modeling The Journal of allergy and clinical immunology High 22322005
2014 HLA-B polymorphisms profoundly influence tapasin dependence of assembly and the stability of peptide-deficient HLA-B forms. Certain HLA-B residues near the C-terminal end of the peptide-binding groove are key determinants of tapasin-independent assembly. Tapasin-independent allotypes assemble more readily with peptides in vitro and show reduced aggregation during refolding compared with tapasin-dependent allotypes of the same supertype. In vitro refolding assays, tapasin-deficient cell line expression, aggregation measurements, cell surface expression and stability assays across 27 HLA-B alleles Journal of immunology High 24790147
2015 KIR3DS1 recognizes HLA-B*57:01 in a peptide-dependent manner. Specific HIV-derived peptides presented by HLA-B*57:01 facilitate productive interactions with KIR3DS1, demonstrating that the peptide repertoire shapes KIR3DS1 engagement and thereby NK cell activation. Structure-driven peptide screening, KIR-HLA binding assays with defined peptide epitopes, functional NK cell assays Journal of virology Medium 25740999
2016 KIR3DL1 and HLA-B Bw4 subtypes calibrate NK cell education and effector capacity in a combinatorial, density-dependent manner. High-density KIR3DL1 paired with Bw4-80I HLA-B confers greatest NK reactivity against HLA-negative targets and HIV-infected CD4+ T cells. Binding strength between KIR3DL1 and HLA-B subtypes, receptor density, and ligand density are each functionally important determinants. Primary NK cell assays with defined KIR3DL1/HLA-B subtype donor combinations, cytotoxicity assays against HIV-infected autologous CD4+ T cells, flow cytometry for receptor/ligand density Journal of immunology Medium 26962229
2016 HIV-1 Nef downregulates HLA-B less efficiently than HLA-A across 46 patient-derived Nef clones. Nef position 202 and the C-terminal CKV motif of HLA-A (absent in HLA-B) contribute to this differential downregulation. A Nef double mutation at positions 202 and the HLA cytoplasmic tail interaction site impairs HLA-A but not HLA-B downregulation, thereby increasing infected cell recognition by HIV-specific T cells. Flow cytometry of HLA surface expression on virus-infected cells, 46 primary Nef clones, site-directed mutagenesis of Nef (N202 variants), co-culture T cell recognition assays, in silico analysis mBio High 26787826
2016 HLA-B*27 subtypes associated with ankylosing spondylitis (B*27:04 and B*27:05) exhibit increased conformational flexibility (molecular dynamics) compared with non-associated subtypes (B*27:06 and B*27:09), as revealed by isotope-edited infrared spectroscopy. Crystal structures show that peptide presentation mode (dual vs. single conformation) does not strictly distinguish disease-associated from non-associated subtypes, whereas elevated molecular dynamics does. X-ray crystallography of pVIPR-HLA-B*27:04 and pVIPR-HLA-B*27:06 complexes, isotope-edited infrared (IR) spectroscopy to probe molecular dynamics Arthritis & rheumatology High 26748477
2017 HLA-B*46:01, formed by intergenic mini-conversion incorporating a segment of HLA-C*01:02, carries the C1 epitope in its α1 domain and is consequently recognized by the C1-specific NK cell receptor KIR2DL3. High-resolution mass spectrometry showed that only the ~21% of HLA-B*46:01 peptides with specific C-terminal characteristics form KIR2DL3 ligands, demonstrating peptide-dependent KIR recognition. High-resolution mass spectrometry immunopeptidomics, KIR2DL3 binding assays with defined peptide subsets, sequence/structure analysis of the mini-conversion Cell reports High 28514659
2017 KIR3DL1 and HLA-B subtype combinations predictive of weak NK inhibition are associated with significantly lower AML relapse and overall mortality after HCT. NK cells expressing strong-inhibitory KIR3DL1 subtypes are reproducibly inhibited by target cells with corresponding HLA-B subtypes in cytotoxic assays, whereas weak/non-inhibitory combinations allow greater cytotoxicity against AML. In vitro NK cytotoxicity assays with segregated KIR3DL1 subtypes and defined HLA-B subtype targets; clinical outcome analysis in 1,328 AML patients post-HCT Journal of clinical oncology High 28520526
2018 HLA-B allotypes show highly variable cell surface expression levels and half-lives on primary lymphocytes, dependent on both allele and cell type. Low expression on lymphocytes for allotypes that bind peptides with Pro at position 2 is linked to TAP disfavoring such peptides; this low-expression phenotype is reversed in monocytes with larger intracellular HLA pools. These allele- and cell-dependent antigen acquisition pathway differences influence surface expression, stability, and receptivity to exogenous antigens. Multicolor flow cytometry, half-life measurements, endogenous peptide binding assays, cell fractionation in primary lymphocytes and monocytes from human donors eLife High 29989547
2018 Approximately 15% of tested HLA-B allotypes (particularly HLA-B*35, HLA-B*57, and HLA-B*15 alleles) are expressed at relatively high levels on the surface of TAP1- or TAP2-deficient cells, indicating TAP-independent assembly. High peptide-loading efficiency, broad specificity for peptides from unconventional sources, and high intrinsic stability of the empty form combinatorially enable TAP-independent assembly. TAP-resistant allotypes are more resistant to viral TAP-inhibitor-induced HLA-I downmodulation and consequent NK activation. Expression of 27 HLA-B alleles in TAP1/TAP2-deficient cell lines, surface expression assays, endoglycosidase H sensitivity, in vitro peptide binding, viral TAP inhibitor challenge, NK activation assays PLoS pathogens High 29995954
2018 Peptide-deficient (empty) HLA-B*35:01 heterodimers are thermostable, detectable on the cell surface, and preferentially bind CD8 via a CD8-dependent mode distinct from peptide-loaded HLA-I/TCR interactions. Empty HLA-B*35:01 tetramers bind a majority of blood-derived CD8+ T cells. These empty conformers do not directly activate CD8+ T cells but accumulate at the immunological synapse, enhance cell adhesion, and amplify cognate peptide-induced CD8+ T cell activation. Tetramer staining of primary CD8+ T cells, immunological synapse imaging, CD8 co-receptor blocking, adhesion and activation assays with peptide-deficient vs. peptide-loaded HLA-B*35:01 eLife High 29741477
2018 CD4+ T cell depletion prior to abacavir (ABC) administration in HLA-B*57:01 transgenic mice converts ABC tolerance into a reactive phenotype: DC maturation is enhanced, systemic ABC-reactive CD8+ T cells with effector/skin-homing phenotype are generated, and CD8+ infiltration occurs in drug-sensitized skin. B7 costimulatory molecule blockade prevents CD8+ T cell activation, placing costimulation as a requirement for the HLA-B*57:01-restricted ABC response. HLA-B*57:01 transgenic mouse model, CD4+ T cell depletion in vivo, DC maturation assays, flow cytometry, skin histology, B7 blockade experiments The Journal of clinical investigation High 29782330
2019 HCMV immunoevasin US11 degrades HLA-A molecules via ERAD but HLA-B locus products generally resist US11-mediated degradation, assemble with β2m, and exit the ER in the presence of US11. A low-complexity region of US11 (between signal peptide and Ig-like domain) is necessary for stable interaction with assembled MHC-I and also responsible for altering the HLA-B ligandome, suggesting a two-pronged viral immune evasion strategy. MHC-I peptide ligand mass spectrometry in HCMV-infected cells, US11 domain mutagenesis, co-immunoprecipitation, intracellular maturation assays PLoS pathogens High 31527904
2019 HLA-B and HLA-C organize differently at the cell surface nanoscale: HLA-C forms larger and more numerous clusters than HLA-B, with a greater proportion of HLA-C contributing to clusters, when expression level is controlled. Both HLA-B and HLA-C form more clusters at lower expression levels. HLA class I organization also varies with cell type (T cells more clustered than B cells). Super-resolution microscopy of three HLA-B allotypes and two HLA-C allotypes transfected into HLA-B/C-negative 721.221 cells, with expression-level controls Frontiers in immunology Medium 30761133
2019 Increased pro-inflammatory cytokine (TNFα/IFNγ) signaling upregulates HLA-B allomorph expression in lung cancer cells, independently driving significant changes in the HLA-bound immunopeptidome beyond those attributable to proteome changes. Quantitative proteomics, immunopeptidomics (LC-MS/MS), cytokine stimulation of lung cancer cells Frontiers in immunology Medium 30833945
2020 HLA-B knockdown in pancreatic cancer cells alters integrin beta-1 (ITGB1) expression and cell migration in a cell-line-dependent manner: HLA-B siRNA increases ITGB1 and migration in S2-013 cells but decreases both in PANC-1 and MIA PaCa-2 cells. A specific transmembrane sequence in the HLA-B heavy chain correlates with the direction of the migration effect. siRNA knockdown of HLA-B in three pancreatic cancer cell lines, transwell migration assays, Western blot for ITGB1 Experimental cell research Medium 32194036
2021 Flucloxacillin (FLX) haptenates lysine residues on HLA-B*57:01-bound peptides, generating drug-modified neoantigens that drive CD8+ T cell responses. FLX-haptenated peptides at P4 and P6 positions are immunogenic in HLA-B*57:01 transgenic mice. FLX also covalently modifies K146 on the HLA-B*57:01 heavy chain itself, potentially interfering with KIR-3DL or peptide interactions. Mass spectrometry immunopeptidomics of FLX-treated B-LCL cells expressing HLA-B*57:01, synthesis and in vivo immunization of drug-conjugated peptides in transgenic mice, CD8+ T cell activation assays Frontiers in immunology High 33633747
2021 Extracellular vesicles over-represent HLA-B complexes and peptide ligands, including cysteinylated peptides, compared with whole cells of the same line. This differential antigen presentation landscape is driven in part by preferential HLA-B sorting into vesicles. HLA-I immunopeptidomics (LC-MS/MS) comparing extracellular vesicles versus whole-cell lysates from the same cell line Communications biology Medium 34211107
2022 Autoimmunity-associated public TCRs using BV9-CDR3β motifs, expanded in AS joints and AAU eyes, recognize self-peptides and microbial peptides presented by HLA-B*27:05 in a shared binding motif. Structural analysis revealed the molecular basis of TCR cross-reactivity between self-antigens and microbial antigens at the HLA-B*27:05 peptide-binding groove. TCR isolation from blood/synovial/ocular T cells, HLA-B*27:05 yeast display peptide libraries, TCR activation assays, structural analysis of peptide-MHC-TCR complexes Nature High 36477533
2010 Large-scale immunopeptidomics of HLA-B*2705 identified 1,268 B27-presented peptides, refining the binding motif and revealing both short canonical peptides and long peptides with bulging middle residues. Human cartilage-derived B27 peptides sharing sequence similarity with common bacterial sequences were identified as molecular mimicry candidates. Recombinant soluble HLA-B27 expression, capillary chromatography/tandem MS, SILAC and iTRAQ quantification from chondrocytic and HeLa cells Arthritis and rheumatism Medium 20112406

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nature genetics 932 12134147
2004 Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 638 15592417
2007 Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nature genetics 616 17496894
2011 Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. The New England journal of medicine 499 21428768
1994 NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules. The Journal of experimental medicine 354 8046332
1979 Assembly and maturation of HLA-A and HLA-B antigens in vivo. Cell 302 93026
1992 Unusual HLA-B alleles in two tribes of Brazilian Indians. Nature 258 1317015
1980 Biosynthesis of HLA-A and HLA-B antigens in vivo. The Journal of biological chemistry 254 7000762
2012 Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome. The Journal of allergy and clinical immunology 226 22322005
2013 Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clinical pharmacology and therapeutics 161 23695185
2014 Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clinical pharmacology and therapeutics 160 25099164
2022 Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides. Nature 132 36477533
1995 Comprehensive, serologically equivalent DNA typing for HLA-B by PCR using sequence-specific primers (PCR-SSP). Tissue antigens 125 7792765
2017 KIR3DL1/HLA-B Subtypes Govern Acute Myelogenous Leukemia Relapse After Hematopoietic Cell Transplantation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 118 28520526
2016 KIR3DL1 and HLA-B Density and Binding Calibrate NK Education and Response to HIV. Journal of immunology (Baltimore, Md. : 1950) 115 26962229
2007 HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated acetylation of p53. Genes & development 111 17403783
1989 Genetic and serological heterogeneity of the supertypic HLA-B locus specificities Bw4 and Bw6. Immunogenetics 108 2777338
1994 HLA-B15: a widespread and diverse family of HLA-B alleles. Tissue antigens 91 7521976
2014 Distinct assembly profiles of HLA-B molecules. Journal of immunology (Baltimore, Md. : 1950) 80 24790147
1997 Episodic evolution and turnover of HLA-B in the indigenous human populations of the Americas. Tissue antigens 76 9331945
1976 HLA-B specificities and w4, w6 specificities are on the same polypeptide. European journal of immunology 75 63373
2018 Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis. Proceedings of the National Academy of Sciences of the United States of America 73 30498034
2015 Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1. Journal of virology 70 25740999
2011 HLA-B*57 Micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control. Journal of virology 69 22090105
1978 Reconstitution of purified detergent-soluble HLA-A and HLA-B antigens into phospholipid vesicles. Proceedings of the National Academy of Sciences of the United States of America 69 356051
1999 HLA-B locus sequence-based typing. Tissue antigens 63 10203021
1993 DNA typing of HLA-B gene in Takayasu's arteritis. Tissue antigens 63 7903491
2012 Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey. Arthritis research & therapy 59 22309845
2010 The HLA-B*2705 peptidome. Arthritis and rheumatism 58 20112406
2020 HLA-B leader and survivorship after HLA-mismatched unrelated donor transplantation. Blood 56 32483623
2018 A transgenic mouse model for HLA-B*57:01-linked abacavir drug tolerance and reactivity. The Journal of clinical investigation 56 29782330
1998 HLA-B*5101 in Greek patients with Behçet's disease. Human immunology 50 9568801
2002 Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients. Annals of the rheumatic diseases 49 12117677
2002 A weak association of HLA-B*2702 with Behçet's disease. Genes and immunity 47 12209364
2019 Pro-inflammatory Cytokines Alter the Immunopeptidome Landscape by Modulation of HLA-B Expression. Frontiers in immunology 44 30833945
2004 Transmission of HIV-1 and HLA-B allele-sharing within serodiscordant heterosexual Zambian couples. Lancet (London, England) 44 15220037
2017 An Update on the Genetic Polymorphism of HLA-B*27 With 213 Alleles Encompassing 160 Subtypes (and Still Counting). Current rheumatology reports 41 28247302
2017 Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease. Current rheumatology reports 40 28386763
2017 The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands. Cell reports 39 28514659
2018 Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity. eLife 38 29989547
2018 The role of HLA-B*27 in spondyloarthritis. Best practice & research. Clinical rheumatology 38 30509441
2005 HLA antigens and post renal transplant lymphoproliferative disease: HLA-B matching is critical. Transplantation 36 16177631
2018 Selected HLA-B allotypes are resistant to inhibition or deficiency of the transporter associated with antigen processing (TAP). PLoS pathogens 34 29995954
1985 HLA-B locus polymorphism: studies with a specific hybridization probe. Proceedings of the National Academy of Sciences of the United States of America 33 3001712
2003 Cloning and sequencing full-length HLA-B and -C genes. Tissue antigens 32 12622774
1998 Familial psoriasis and HLA-B: unambiguous support for linkage in 97 published families. Human heredity 32 9694251
2014 Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population. PloS one 29 25019531
2021 Alterations in the HLA-B*57:01 Immunopeptidome by Flucloxacillin and Immunogenicity of Drug-Haptenated Peptides. Frontiers in immunology 28 33633747
2020 Identification of Flucloxacillin-Haptenated HLA-B*57:01 Ligands: Evidence of Antigen Processing and Presentation. Toxicological sciences : an official journal of the Society of Toxicology 28 32726429
2019 A three-platelet mRNA set: MAX, MTURN and HLA-B as biomarker for lung cancer. Journal of cancer research and clinical oncology 28 31552488
2018 Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function. eLife 28 29741477
2017 Novel genetic loci associated HLA-B*08:01 positive myasthenia gravis. Journal of autoimmunity 26 29037440
2016 Increased Conformational Flexibility of HLA-B*27 Subtypes Associated With Ankylosing Spondylitis. Arthritis & rheumatology (Hoboken, N.J.) 26 26748477
2016 HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption. Epilepsia 26 27666425
2011 KIR3DL1+HLA-B Bw4Ile80 and KIR2DS1+HLA-C2 combinations are both associated with ankylosing spondylitis in the Iranian population. International journal of immunogenetics 26 21797986
2021 HLA-B and cysteinylated ligands distinguish the antigen presentation landscape of extracellular vesicles. Communications biology 25 34211107
2018 HLA-B*27 subtypes and their implications in the pathogenesis of ankylosing spondylitis. Gene 25 29803000
2017 Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype. The Journal of infectious diseases 25 28968792
2000 DNA sequencing of HLA-B alleles in Mexican patients with Takayasu arteritis. International journal of cardiology 25 10980349
2023 The Gut Microbiota Metabolite Urolithin B Prevents Colorectal Carcinogenesis by Remodeling Microbiota and PD-L1/HLA-B. Oxidative medicine and cellular longevity 24 36778211
2023 HLA-B*27 and Ankylosing Spondylitis: 50 Years of Insights and Discoveries. Current rheumatology reports 24 37950822
2018 Identification of Native and Posttranslationally Modified HLA-B*57:01-Restricted HIV Envelope Derived Epitopes Using Immunoproteomics. Proteomics 24 29437277
1997 Frequencies of HLA-A and HLA-B alleles in a Mexico City mestizo sample. American journal of human biology : the official journal of the Human Biology Council 24 28561491
1997 Interactions of HLA-B*4801 with peptide and CD8. Tissue antigens 24 9331948
2020 Polymorphisms of HLA-B: influences on assembly and immunity. Current opinion in immunology 22 32619904
2015 Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function. Journal of virology 22 26355081
1994 HLA-B alleles and complotypes in Mexican patients with seronegative spondyloarthropathies. Annals of the rheumatic diseases 22 7826137
2022 Assessment of HLA-B genetic variation with an HLA-B leader tool and implications in clinical transplantation. Blood advances 21 34529780
2021 The enigmatic role of HLA-B*27 in spondyloarthritis pathogenesis. Seminars in immunopathology 21 33481054
2014 Structural and electrostatic analysis of HLA B-cell epitopes: inference on immunogenicity and prediction of humoral alloresponses. Current opinion in organ transplantation 20 24977436
2013 HLA B*5701 status, disease progression, and response to antiretroviral therapy. AIDS (London, England) 20 23921616
2013 HIV subtype influences HLA-B*07:02-associated HIV disease outcome. AIDS research and human retroviruses 20 24010680
1997 Inverse correlation between expression of HLA-B and c-myc in uveal melanoma. The Journal of pathology 20 9072006
2010 Impaired cell surface expression of HLA-B antigens on mesenchymal stem cells and muscle cell progenitors. PloS one 19 20531935
2001 HLA-A and HLA-B transcription decrease with ageing in peripheral blood leucocytes. Clinical and experimental immunology 19 11529916
1998 HLA-B*27 subtyping by PCR-RFLP in Spanish patients with ankylosing spondylitis. Tissue antigens 19 9864041
2021 HLA-B*15 predicts survival in Egyptian patients with COVID-19. Human immunology 18 34607724
2018 Multiplexed Nanopore Sequencing of HLA-B Locus in Māori and Pacific Island Samples. Frontiers in genetics 18 29760718
2009 MICA polymorphisms and haplotypes with HLA-B and HLA-DRB1 in Koreans. Tissue antigens 18 19895570
2024 Mucosal signatures of pathogenic T cells in HLA-B*27+ anterior uveitis and axial spondyloarthritis. JCI insight 17 39024572
2016 HLA-B*51:01 is strongly associated with clindamycin-related cutaneous adverse drug reactions. The pharmacogenomics journal 16 27527109
2015 Detection of HLA-B*58:01 with TaqMan assay and its association with allopurinol-induced sCADR. Clinical chemistry and laboratory medicine 16 25257159
2013 Increased expression of intrinsic antiviral genes in HLA-B*57-positive individuals. Journal of leukocyte biology 16 23929683
2009 Assembly and intracellular trafficking of HLA-B*3501 and HLA-B*3503. Immunogenetics 16 19838694
2016 Relative Resistance of HLA-B to Downregulation by Naturally Occurring HIV-1 Nef Sequences. mBio 15 26787826
1998 Molecular, serological and population studies on a novel HLA-B allele--HLA-B*5002. Tissue antigens 15 9694362
1998 Novel HLA-A and HLA-B alleles. Tissue antigens 15 9714480
2022 HLA-B*07:02 and HLA-C*07:02 are associated with trimethoprim-sulfamethoxazole respiratory failure. The pharmacogenomics journal 14 35169303
2019 HLA-B locus products resist degradation by the human cytomegalovirus immunoevasin US11. PLoS pathogens 14 31527904
2021 The HLA Ligandome Comprises a Limited Repertoire of O-GlcNAcylated Antigens Preferentially Associated With HLA-B*07:02. Frontiers in immunology 13 34925382
2020 HLA-B influences integrin beta-1 expression and pancreatic cancer cell migration. Experimental cell research 13 32194036
1999 HLA-B*4703: sequence confirmation, serology and distribution. Tissue antigens 13 10395111
2022 Allelic imbalance of HLA-B expression in human lung cells infected with coronavirus and other respiratory viruses. European journal of human genetics : EJHG 12 35322240
2019 HLA-B*44:138Q: Evidence for a confined deletion and recombination events in an otherwise unaffected HLA-haplotype. HLA 11 30488584
2019 HLA-B and HLA-C Differ in Their Nanoscale Organization at Cell Surfaces. Frontiers in immunology 11 30761133
2006 Low-cost, simultaneous, single-sequence genotyping of the HLA-A, HLA-B and HLA-C loci. Tissue antigens 11 16774537
2004 HLA-Cw*0409N is associated with HLA-A*2301 and HLA-B*4403-carrying haplotypes. Human immunology 11 14969773
2011 HLA-B*27 allele associated to Behçet's disease and to anterior uveitis in Moroccan patients. Annales de biologie clinique 10 21896406
2021 Association between the HLA-B*1502 gene and mild maculopapular exanthema induced by antiepileptic drugs in Northwest China. BMC neurology 9 34488672
1996 Ligation based HLA-B*27 typing. Tissue antigens 9 8896172

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