Affinage

HLA-F

HLA class I histocompatibility antigen, alpha chain F · UniProt P30511

Length
346 aa
Mass
39.1 kDa
Annotated
2026-06-10
87 papers in source corpus 25 papers cited in narrative 24 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-F is a non-classical MHC class Ib molecule encoded by a class I gene with a shortened cytoplasmic tail and an antigen-binding groove divergent from classical class I, displaying a tissue-restricted expression pattern (PMID:1688605, PMID:1707659). It is synthesized as a β2-microglobulin-associated heavy chain that is retained predominantly in the ER as an empty, peptide-free heterodimer in association with the conventional class I assembly machinery TAP and calreticulin (PMID:10605026). Unlike classical class I, ER export of HLA-F is governed entirely by its cytoplasmic tail through a C-terminal valine that engages the COPII coat and an RxR motif that binds 14-3-3 proteins (PMID:16709803), and its surface delivery proceeds through both tapasin-dependent and tapasin-independent routes (PMID:14607927). HLA-F is intracellular in resting lymphocytes, NK cells, and monocytes but translocates to the surface upon lymphocyte activation, where it is displayed largely as an open conformer (free heavy chain) that physically associates with peptide-free MHC-I heavy chains (PMID:20865824, PMID:20483783). In this open-conformer state HLA-F is the high-affinity ligand for the activating NK receptor KIR3DS1, and ligation triggers degranulation and antiviral cytokine production by primary NK cells; this axis drives NK-cell control of HIV-1 and HCV, and HLA-F is upregulated on cells infected with HIV, HCV, BK polyomavirus, and Japanese encephalitis virus, the latter via NF-κB (PMID:27455421, PMID:27649529, PMID:31270222, PMID:30031767, PMID:25461528, PMID:33359499). HLA-F open conformers also bind the inhibitory receptors ILT2 and ILT4 (PMID:11169396). Although it can present non-canonical-length peptides (8–24 residues with C-terminal lysine preference), peptide loading abolishes KIR3DS1 binding, and HIV-derived hemoglobin peptides dominant in infected cells reduce KIR3DS1 engagement, providing a route to immune evasion (PMID:27455421, PMID:30941482, PMID:31717259, PMID:33126487). Beyond immune surveillance, HLA-F drives trophoblast proliferation and invasion by promoting glycolysis through PKM2 — binding the PKM promoter to upregulate transcription and reducing K305 lactylation to enhance enzymatic activity — and analogously stabilizes HK2 to fuel aerobic glycolysis and proliferation in glioma cells (PMID:33867844, PMID:40251569, PMID:37854606).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1990 High

    Established that HLA-F is a distinct class I gene rather than a classical HLA allele, defined by a shortened cytoplasmic tail, altered groove residues, and restricted tissue expression.

    Evidence Gene/protein sequencing, RNase protection, Northern analysis, and cDNA transfection with immunolocalization in B cell lines

    PMID:1688605 PMID:1707659

    Open questions at the time
    • Did not establish function or surface ligand
    • Intracellular retention mechanism not yet defined
  2. 2000 High

    Showed HLA-F is an ER-retained, peptide-empty β2m heterodimer engaged with the classical assembly machinery, posing the question of why it does not reach the surface like classical class I.

    Evidence Recombinant refolding, endoglycosidase H sensitivity, thermostability assay, and co-IP with TAP and calreticulin

    PMID:10605026

    Open questions at the time
    • Trigger for surface translocation unknown
    • Functional consequence of empty heterodimer not defined
  3. 2000 High

    Identified the first receptors for HLA-F by showing it binds the inhibitory ILT2 and ILT4, establishing HLA-F as a functional ligand.

    Evidence Tetramer staining of monocytes/B cells, receptor transfection, and surface plasmon resonance

    PMID:11169396

    Open questions at the time
    • Conformational state of HLA-F required for binding not yet resolved
    • Downstream signaling not addressed
  4. 2000 Medium

    Defined the transcriptional control of HLA-F as responsive to NF-κB, IFN-γ/ISRE, and CIITA, distinguishing it from HLA-G and HLA-E.

    Evidence Promoter analysis and reporter transactivation assays

    PMID:11137213

    Open questions at the time
    • Endogenous physiological inducers not tested
    • Link between transcription and surface protein not established
  5. 2003 High

    Resolved that surface HLA-F arrives by two pathways — a TAP-independent, tapasin-independent endoH-sensitive route and a tapasin-dependent endoH-resistant route — separating it from canonical class I trafficking.

    Evidence Flow cytometry and endoH assays in TAP- and tapasin-deficient cell lines

    PMID:14607927

    Open questions at the time
    • Molecular machinery driving export not identified
    • Functional difference between the two surface forms unclear
  6. 2006 High

    Identified the cytoplasmic tail motifs controlling HLA-F ER export, explaining how its trafficking is uncoupled from classical class I.

    Evidence Tail mutagenesis with surface expression assays and binding to COPII and 14-3-3 proteins

    PMID:16709803

    Open questions at the time
    • Signal that initiates tail-dependent export upon activation unknown
    • Regulation of 14-3-3 engagement not defined
  7. 2010 High

    Demonstrated that HLA-F surfaces upon lymphocyte activation as a peptide-free open conformer that associates specifically with open (peptide-free) MHC-I heavy chains, defining its conformational identity.

    Evidence Activation of primary lymphocytes, reciprocal surface/intracellular staining, co-IP, SPR, and tetramer colocalization

    PMID:20483783 PMID:20865824

    Open questions at the time
    • Activating NK receptor for the open conformer not yet identified
    • Significance of regulatory T cell exclusion from upregulation unclear
  8. 2013 High

    Established HLA-F as a prototypical MHC-I open-conformer ligand for KIR receptors, showing KIR3DL2 and KIR2DS4 engage peptide-free HLA-F.

    Evidence SPR, cell binding, and functional NK cell assays

    PMID:24018270

    Open questions at the time
    • Did not yet identify the dominant high-affinity activating receptor
    • In vivo relevance not addressed
  9. 2013 Medium

    Described a TAP/tapasin-independent, lysosome-dependent cross-presentation pathway involving HLA-F and MHC-I open conformers on activated cells.

    Evidence In vitro cross-presentation assays with TAP/tapasin/lysosomal inhibition in activated lymphocyte and monocyte models

    PMID:23851683

    Open questions at the time
    • Single-lab in vitro pathway dissection
    • Physiological contribution of this pathway unquantified
  10. 2016 High

    Identified KIR3DS1 as the high-affinity activating receptor for HLA-F open conformers and linked the interaction to NK-cell control of HIV-1, with HIV reducing KIR3DS1 binding as evasion.

    Evidence Screen of 100 class I proteins, SPR, primary NK degranulation/cytokine assays, HIV-1 replication assays, and biochemical pulldown/granule exocytosis

    PMID:27455421 PMID:27649529

    Open questions at the time
    • Structural basis of KIR3DS1/HLA-F recognition not solved
    • In vivo NK control quantification limited
  11. 2018 High

    Confirmed that HLA-F engagement is sufficient to activate KIR3DS1+ NK cells using independent blocking reagents and HLA-null cell systems, including against HIV-infected and HCV-infected cells.

    Evidence Co-culture with HIV-infected CD4+ T cells and HLA-null transfectants, KIR3DS1-Fc and anti-HLA-F blocking, intracellular cytokine staining, plus HCV culture and humanized models

    PMID:29743316 PMID:30031767 PMID:31270222

    Open questions at the time
    • Mechanistic detail for HCV control limited
    • Quantitative contribution in vivo not fully resolved
  12. 2019 Medium

    Characterized the HLA-F peptide repertoire (non-canonical 8–24 aa, C-terminal Lys, allele-specific sources) and showed peptide loading abolishes KIR3DS1 binding, with HIV-derived hemoglobin peptides reducing engagement.

    Evidence Soluble HLA complex recovery, LC-MS peptide elution, recombinant expression, KIR3DS1-Fc binding, and HIV+ vs HIV- proteome comparison

    PMID:30941482 PMID:31717259 PMID:33126487

    Open questions at the time
    • Single lab for peptide elution studies
    • Physiological role of peptide-loaded HLA-F unclear
  13. 2018 Medium

    Extended HLA-F induction to multiple infection and physiological contexts, identifying NF-κB-driven induction by JEV/TNF-α and a progesterone-responsive enhancer creating a GATA2 site that loops to the promoter to elevate endometrial expression.

    Evidence shRNA knockdown of p65, luciferase reporters, eQTL analysis, and chromatin conformation capture in endometrial cells

    PMID:25461528 PMID:30245028

    Open questions at the time
    • Single-lab regulatory studies
    • Connection between transcriptional induction and functional surface display not always demonstrated
  14. 2020 Medium

    Showed BK polyomavirus upregulates surface HLA-F in kidney tubular cells and nephropathy biopsies, increasing KIR3DS1 binding and NK activation, broadening the antiviral surveillance role.

    Evidence In vitro infection model, flow cytometry, primary NK activation assays, and kidney biopsy immunostaining

    PMID:33359499

    Open questions at the time
    • Causal role in nephropathy outcome not established
    • Single-lab validation
  15. 2025 Medium

    Revealed a cell-intrinsic, non-immune function in which HLA-F drives proliferation through glycolysis — in trophoblasts via PKM promoter binding and PKM2 K305 delactylation, and analogously via HK2 stabilization in glioma.

    Evidence ChIP-seq, 4D label-free proteomics, overexpression/knockdown with PKM2 or HK2 rescue, glycolysis and proliferation assays, and xenograft/Mini-PDX models

    PMID:33867844 PMID:37854606 PMID:40251569

    Open questions at the time
    • Mechanism by which an MHC molecule accesses chromatin to bind the PKM promoter not explained
    • Single-lab studies for each system
    • Relationship between surface-ligand and intracellular metabolic functions undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HLA-F reconciles its dual identities — surface open-conformer ligand for KIR3DS1/ILT receptors versus an intracellular regulator of glycolytic gene expression — and the structural basis of KIR3DS1 recognition remain unresolved.
  • No crystal/cryo-EM structure of HLA-F/KIR3DS1 in the timeline
  • Mechanism linking nuclear/chromatin function to a class I cell-surface molecule unexplained
  • Whether peptide-loaded and open-conformer pools are interconverted in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0003677 DNA binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 3 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-1643685 Disease 3 R-HSA-1430728 Metabolism 2
Partners
B2MCALRKIR3DL2KIR3DS1LILRB1LILRB2TAPYWHA?

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 HLA-F (HLA-5.4) encodes an intact class I protein with a shortened cytoplasmic tail, five altered residues in the antigen-binding groove (three non-conservative), and a 3' untranslated region containing a novel multigene family. The gene is expressed in B lymphoblastoid cell lines, resting T cells, and skin cells but not in the T cell line Molt 4, indicating a tissue-specific expression pattern distinct from classical class I genes. Gene sequencing, RNase protection assay, Northern analysis, protein sequence analysis The Journal of experimental medicine High 1688605
1990 HLA-F (Dew3) protein expressed after transfection into a human EBV-transformed B cell line is located intracellularly. The transcribed mRNA is shorter than classical class I mRNAs due to an altered acceptor splice site that removes exon 7. Expression is restricted to B cell lines and peripheral blood lymphocytes and is absent from T cell lines, fibroblasts, and myelomonocytic leukaemia. cDNA cloning, transfection, immunolocalization, tissue expression analysis International immunology Medium 1707659
2000 HLA-F heavy chain refolded with β2-microglobulin forms a stable complex. HLA-F is predominantly intracellular, contains an immature (endoglycosidase H-sensitive) oligosaccharide indicating ER retention, and thermostability assays indicate it is expressed as an empty heterodimer devoid of peptide. HLA-F associates with calreticulin and TAP, components of the conventional class I assembly pathway, yet IFN-γ treatment induces HLA-F mRNA and protein without producing cell surface expression. Recombinant protein refolding, immunoprecipitation, endoglycosidase H assay, thermostability assay, Western blot, flow cytometry Journal of immunology High 10605026
2000 HLA-F tetramers (HLA-F heavy chain refolded with β2-microglobulin) bind peripheral blood monocytes and B cells. Transfection of the inhibitory receptors ILT2 (LIR1) and ILT4 (LIR2) into non-binding cells confers HLA-F tetramer binding. Surface plasmon resonance demonstrated a direct molecular interaction between HLA-F and ILT2 and ILT4. Recombinant protein refolding, tetramer staining, transfection, surface plasmon resonance European journal of immunology High 11169396
2000 HLA-F gene transcription is inducible by NF-κB through the κB1 site of enhancer A, is responsive to IFN-γ through the ISRE element, and is inducible by CIITA through the SXY regulatory module, distinguishing its transcriptional regulation from HLA-G (which lacks responsiveness to NF-κB, IRF1, and CIITA) and from HLA-E. Promoter sequence analysis, transactivation assays (reporter gene/functional promoter studies) Human immunology Medium 11137213
2003 HLA-F surface expression on B lymphoblastoid and monocyte cell lines is independent of TAP function. Of the two glycosylation forms detected on the surface, an endoglycosidase H-sensitive form is tapasin-independent, whereas an endoglycosidase H-resistant form is tapasin-dependent, indicating two distinct pathways to the cell surface. Flow cytometry, endoglycosidase H assay, analysis of TAP-deficient and tapasin-deficient cell lines Journal of immunology High 14607927
2006 HLA-F export from the endoplasmic reticulum (ER) depends entirely on its cytoplasmic tail, unlike classical class I molecules. Two export motifs were identified: a C-terminal valine residue that functions in ER export and interacts with COPII coat complex, and an RxR motif that plays an important role in anterograde transport and binds 14-3-3 proteins. Deletion and point mutagenesis of cytoplasmic tail, cell surface expression assays, binding assays for COPII and 14-3-3 proteins Journal of immunology High 16709803
2010 HLA-F is expressed intracellularly in resting B cells, T cells, NK cells, and monocytes but translocates to the cell surface upon lymphocyte activation. CD4+CD25+ regulatory T cells do not upregulate surface HLA-F upon activation, whereas CD4+CD25- T cells show strong surface HLA-F induction. Individuals genetically deficient for TAP or tapasin show the same activation-induced surface expression profile but with altered kinetics. Western blot, flow cytometry, activation of primary lymphocytes, analysis of TAP/tapasin-deficient donors European journal of immunology High 20865824
2010 HLA-F on the surface of B lymphoblastoid cells and activated lymphocytes is expressed as an open conformer without bound peptide. HLA-F physically interacts with MHC class I heavy chain only when the heavy chain is in the open conformer (peptide-free) form; trimeric (peptide-loaded) MHC-I does not interact. This interaction was demonstrated by co-immunoprecipitation and surface plasmon resonance, and indirectly confirmed by coincident tetramer and MHC-I heavy chain colocalization on cell surfaces. Co-immunoprecipitation, surface plasmon resonance, peptide-binding profiling, tetramer colocalization, perturbation of MHC-I structure Journal of immunology High 20483783
2013 KIR3DL2 and KIR2DS4 physically and functionally interact with HLA-F expressed as a free open conformer devoid of peptide. Classical MHC-I open conformers also serve as ligands, defining HLA-F as a prototypical MHC-I open conformer ligand for KIR receptors. Surface plasmon resonance, functional NK cell assays, cell binding experiments Journal of immunology High 24018270
2013 HLA-F and MHC-I open conformers on activated cells participate in a TAP- and tapasin-independent cross-presentation pathway for exogenous proteins, sensitive to inhibitors of lysosomal enzymes and dependent on MHC-I allotype-specific epitope recognition for antigen uptake. In vitro antigen cross-presentation assays, inhibition of TAP/tapasin/lysosomal enzymes, activated lymphocyte and monocyte models Journal of immunology Medium 23851683
2016 KIR3DS1 binds HLA-F open conformers (not peptide-loaded HLA-F) with high affinity; this was confirmed biochemically and functionally. Primary KIR3DS1+ NK cells degranulate and produce antiviral cytokines upon encountering HLA-F and inhibit HIV-1 replication in vitro. Activation of CD4+ T cells induces surface HLA-F expression, enabling KIR3DS1 binding; HIV-1 infection further increases HLA-F transcription but decreases KIR3DS1 binding, suggesting immune evasion. Screening of 100 HLA class I proteins, surface plasmon resonance, primary NK cell degranulation assay, cytokine production assay, HIV-1 replication assay, flow cytometry Nature immunology High 27455421
2016 KIR3DS1 but not KIR3DL1 physically binds HLA-F open conformers and other MHC-I open conformers, as measured by surface plasmon resonance. This was confirmed by biochemical pulldown from cell lines and heterodimerization experiments with recombinant proteins. KIR3DS1 ligation by HLA-F triggers granule exocytosis in activated NK cells. Surface plasmon resonance, biochemical pulldown, recombinant protein heterodimerization, granule exocytosis assay PloS one High 27649529
2018 KIR3DS1 on primary NK cells is activated by HLA-F expressed on HIV-infected CD4+ T cells. Blocking the HLA-F/KIR3DS1 interaction with KIR3DS1-Fc chimeric protein or anti-HLA-F monoclonal antibody reduces the frequency of activated KIR3DS1+ NK cells, directly demonstrating that the HLA-F/KIR3DS1 interaction is sufficient to trigger NK cell functions including CCL4, IFN-γ, and CD107a expression. Co-culture of HIV-infected CD4+ T cells with primary NK cells, blocking antibody experiments, intracellular cytokine staining, flow cytometry Journal of virology High 31270222
2018 HLA-F expressed on HLA-null 721.221 cells (both untreated and acid-pulsed) activates primary KIR3DS1+ NK cells for CCL4/IFN-γ secretion and CD107a expression. Blocking the HLA-F/KIR3DS1 interaction reduces this activation, confirming that HLA-F ligation is sufficient to activate KIR3DS1+ NK cells. Transfection of HLA-null cells, co-culture with primary NK cells, blocking antibody and KIR3DS1-Fc experiments, flow cytometry Journal of immunology High 29743316
2018 KIR3DS1/HLA-F interaction contributes to NK cell-mediated control of HCV replication. HLA-F is upregulated on HCV-infected cells, and interactions between KIR3DS1 and HLA-F activate NK cells to control HCV in cell culture. In vitro HCV cell culture, humanized mouse liver models, primary liver biopsy analysis, NK cell functional assays Gastroenterology Medium 30031767
2019 HLA-F*01:01 presents peptides of non-canonical length (preferred length of 16 residues) without a defined N-terminal anchor. Stable peptide-HLA-F*01:01 complexes were recovered and peptide characteristics were analyzed; source proteins of HLA-F-restricted peptides are predominantly described as interacting with HIV proteins. Stable pHLA-F*01:01 complex recovery, mass spectrometry peptide analysis Immunogenetics Medium 30941482
2019 HLA-F allelic variants (F*01:01, F*01:03, F*01:04) present peptides with 8–24 amino acid length and C-terminal Lys preference, but with no overlap in proteomic source between allelic variants despite being selected from the same cellular content. Recombinant soluble KIR3DS1 does not bind peptide-loaded HLA-F complexes but binds when HLA-F is in the open conformer form (after acid elution of peptides), and hemoglobin peptides dominant in HIV-infected CD4+ T cells reduce KIR3DS1 binding to HLA-F. Soluble HLA technology, LC-MS peptide analysis, K562 cell recombinant expression, KIR3DS1-Fc binding assay, proteome analysis of CD4+/HIV+ vs CD4+/HIV- cells International journal of molecular sciences / International journal of molecular sciences Medium 31717259 33126487
2014 HLA-F gene expression is induced by Japanese encephalitis virus (JEV) infection through NF-κB. shRNA-mediated knockdown of the p65 subunit of NF-κB inhibited JEV-induced HLA-F expression in amniotic and human brain microvascular endothelial cell lines. TNF-α treatment also induced HLA-F expression via NF-κB, confirmed by luciferase reporter assays using HLA-F enhancer A elements. shRNA knockdown, luciferase reporter assay, Western blot, RT-PCR Virology Medium 25461528
2020 BK polyomavirus infection significantly increases surface expression of HLA-F on kidney tubular cells in vitro and in kidney biopsy samples from patients with BK polyomavirus-associated nephropathy. Upregulated HLA-F increases KIR3DS1 binding to infected cells and activates primary KIR3DS1+ NK cells. In vitro BK polyomavirus infection model, flow cytometry, primary NK cell activation assays, kidney biopsy immunostaining Kidney international Medium 33359499
2018 A derived A allele at SNP rs2523393 in a distal enhancer of HLA-F creates a GATA2 binding site in a progesterone-responsive enhancer that physically loops to the HLA-F promoter. This results in increased HLA-F expression. HLA-F expression is upregulated in the endometrium during the window of implantation and by progesterone in decidual stromal cells. eQTL analysis (GTEx replication), luciferase reporter assay, chromatin conformation capture (enhancer-promoter looping), GATA2 binding assay, endometrial cell culture with progesterone treatment American journal of human genetics Medium 30245028
2021 Forced expression of HLA-F in glioma cells promoted aerobic glycolysis via increased HK2 (hexokinase 2) protein stabilization; silencing HK2 reduced HLA-F-mediated glycolysis and cell proliferation. Anti-HLA-F antibody treatment suppressed growth of HLA-F-expressing cells in immunodeficient mice. Lentiviral overexpression, shRNA knockdown, in vitro glycolysis assays, xenograft tumor model, anti-HLA-F antibody treatment International journal of biological sciences Medium 33867844
2025 HLA-F promotes trophoblast proliferation via PKM2-dependent glycolysis. HLA-F overexpression increases PKM2 protein expression and enzymatic activity, enhancing glycolysis. Mechanistically, HLA-F binds the PKM gene promoter (shown by ChIP-seq) to upregulate PKM2 transcription, and also promotes PKM2 activity by downregulating lactylation at residue K305. Silencing PKM2 abrogates HLA-F-mediated glycolysis and proliferation. HLA-F expression is reduced in preeclamptic trophoblasts. ChIP-seq, 4D label-free quantitative proteomics, overexpression/siRNA knockdown, glycolysis assays, CCK8/MTT/colony formation, Mini-PDX model Molecular medicine Medium 40251569
2023 HLA-F overexpression in trophoblast (Jar) cells promotes cell proliferation, invasion, and migration, while knockdown inhibits these functions. In NK-92MI cells, HLA-F overexpression increases secretion of immunoregulatory cytokines CSF1 and CCL22 and promotes adaptive NKG2C+ NK cell transformation. Lentiviral overexpression, siRNA knockdown, proliferation/invasion/migration assays, cytokine measurement, flow cytometry for NK cell phenotype Frontiers in immunology Medium 37854606

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. Human immunology 225 2249951
1990 Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element. The Journal of experimental medicine 201 1688605
2016 Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. Nature immunology 191 27455421
2000 Functional characterization of HLA-F and binding of HLA-F tetramers to ILT2 and ILT4 receptors. European journal of immunology 159 11169396
1998 Structure and function of the human MHC class Ib molecules HLA-E, HLA-F and HLA-G. Immunological reviews 142 9700506
2017 Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition. American journal of reproductive immunology (New York, N.Y. : 1989) 126 28185362
1996 Identification of seven new human MHC class I region genes around the HLA-F locus. Immunogenetics 120 8662070
2013 HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors. Journal of immunology (Baltimore, Md. : 1950) 119 24018270
2000 Transcriptional regulation of the MHC class Ib genes HLA-E, HLA-F, and HLA-G. Human immunology 115 11137213
2016 HLA-F and MHC-I Open Conformers Bind Natural Killer Cell Ig-Like Receptor KIR3DS1. PloS one 98 27649529
2010 HLA-F is a surface marker on activated lymphocytes. European journal of immunology 93 20865824
1992 Cloning and physical mapping of the HLA class I region spanning the HLA-E-to-HLA-F interval by using yeast artificial chromosomes. Proceedings of the National Academy of Sciences of the United States of America 92 1557372
2000 HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib protein with a restricted expression pattern. Journal of immunology (Baltimore, Md. : 1950) 88 10605026
2006 Selective export of HLA-F by its cytoplasmic tail. Journal of immunology (Baltimore, Md. : 1950) 73 16709803
2003 HLA-F surface expression on B cell and monocyte cell lines is partially independent from tapasin and completely independent from TAP. Journal of immunology (Baltimore, Md. : 1950) 69 14607927
2010 HLA-F complex without peptide binds to MHC class I protein in the open conformer form. Journal of immunology (Baltimore, Md. : 1950) 67 20483783
2013 HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway. Journal of immunology (Baltimore, Md. : 1950) 52 23851683
1993 Characterization of the rhesus macaque (Macaca mulatta) equivalent of HLA-F. Immunogenetics 52 8482576
2019 HLA-F-AS1/miR-330-3p/PFN1 axis promotes colorectal cancer progression. Life sciences 50 31863778
2006 HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the nonclassical class I genes. Immunogenetics 49 16570139
2006 The surface expression of HLA-F on decidual trophoblasts increases from mid to term gestation. Journal of reproductive immunology 48 16806485
1992 A continuous restriction map from HLA-E to HLA-F. Structural comparison between different HLA-A haplotypes. Immunogenetics 48 1537609
2012 Alteration of HLA-F and HLA I antigen expression in the tumor is associated with survival in patients with esophageal squamous cell carcinoma. International journal of cancer 45 22544725
1993 Linkage analysis of 6p21 polymorphic markers and the hereditary hemochromatosis: localization of the gene centromeric to HLA-F. Human molecular genetics 45 8518796
2015 Human leukocyte antigen (HLA)-E and HLA-F expression in gastric cancer. Anticancer research 44 25862890
2008 Natural-killer cell ligands at the maternal-fetal interface: UL-16 binding proteins, MHC class-I chain related molecules, HLA-F and CD48. Human reproduction (Oxford, England) 44 18658158
2018 Interactions Between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture. Gastroenterology 41 30031767
2016 Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies HLA-F and TAP2 as Fecundability-Associated Genes. PLoS genetics 40 27447835
2019 Correlation of alteration of HLA-F expression and clinical characterization in 593 brain glioma samples. Journal of neuroinflammation 38 30755240
2015 Clinical implication of human leukocyte antigen (HLA)-F expression in breast cancer. Pathology international 35 26332651
2021 LncRNA HLA-F-AS1 promotes colorectal cancer metastasis by inducing PFN1 in colorectal cancer-derived extracellular vesicles and mediating macrophage polarization. Cancer gene therapy 33 33531647
2023 Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia. Frontiers in immunology 30 37854606
2019 A role for both HLA-F and HLA-G in reproduction and during pregnancy? Human immunology 29 31558330
2018 An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F. American journal of human genetics 29 30245028
1995 Three highly polymorphic microsatellites at the human myelin oligodendrocyte glycoprotein locus, 100 kb telomeric to HLA-F. Characterization and relation to HLA haplotypes. Human immunology 29 7499175
2022 Endometrial HLA-F expression is influenced by genotypes and correlates differently with immune cell infiltration in IVF and recurrent implantation failure patients. Human reproduction (Oxford, England) 26 35689445
1996 Structural analysis of the HLA-A/HLA-F subregion: precise localization of two new multigene families closely associated with the HLA class I sequences. Genomics 26 8833150
2022 Human leukocyte antigen HLA-C, HLA-G, HLA-F, and HLA-E placental profiles are altered in early severe preeclampsia and preterm birth with chorioamnionitis. American journal of obstetrics and gynecology 23 35863458
2020 Variation in the HLA-F gene locus with functional impact is associated with pregnancy success and time-to-pregnancy after fertility treatment. Human reproduction (Oxford, England) 23 32020202
2022 HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation. Cancer genomics & proteomics 22 35181585
2016 HLA-F coding and regulatory segments variability determined by massively parallel sequencing procedures in a Brazilian population sample. Human immunology 22 27448841
2021 Targeting HLA-F suppresses the proliferation of glioma cells via a reduction in hexokinase 2-dependent glycolysis. International journal of biological sciences 20 33867844
2019 HLA-F on Autologous HIV-Infected Cells Activates Primary NK Cells Expressing the Activating Killer Immunoglobulin-Like Receptor KIR3DS1. Journal of virology 20 31270222
2015 Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies. Clinical and experimental immunology 20 26440212
2022 LncRNA HLA-F-AS1 attenuates the ovarian cancer development by targeting miR-21-3p/PEG3 axis. Anti-cancer drugs 19 35276697
1996 Systematic sequencing of the human HLA-A/HLA-F region: establishment of a cosmid contig and identification of a new gene cluster within 37 kb of sequence. Genomics 19 8938444
2013 Characterization of HLA-F polymorphism in four distinct populations in Mainland China. International journal of immunogenetics 18 23551590
1990 The human class I MHC gene HLA-F is expressed in lymphocytes. International immunology 18 1707659
2020 HLA-G and HLA-F protein isoform expression in breast cancer patients receiving neoadjuvant treatment. Scientific reports 17 32978482
2004 Detection of anti-HLA-F antibodies in sera from cancer patients. Anticancer research 17 15515436
2018 Non-classical human leucocyte antigens in ankylosing spondylitis: possible association with HLA-E and HLA-F. RMD open 16 30018800
2018 Human leukocyte antigen (HLA-F) polymorphism is associated with chronic HBV infection. 3 Biotech 15 29354360
2018 HLA-F on HLA-Null 721.221 Cells Activates Primary NK Cells Expressing the Activating Killer Ig-like Receptor KIR3DS1. Journal of immunology (Baltimore, Md. : 1950) 15 29743316
1996 Physical map of the HLA-A/HLA-F subregion and identification of two new coding sequences. Immunogenetics 15 8575815
1995 Characterization of a recombinant that locates the hereditary hemochromatosis gene telomeric to HLA-F. Human genetics 15 7649553
2021 STAT3-induced HLA-F-AS1 promotes cell proliferation and stemness characteristics in triple negative breast cancer cells by upregulating TRABD. Bioorganic chemistry 14 33618253
2019 HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues. Immunogenetics 14 30941482
2020 Examining extended human leukocyte antigen-G and HLA-F haplotypes: the HLA-G UTR-4 haplotype is associated with shorter time to pregnancy in an infertility treatment setting when both female and male partners are carriers. Fertility and sterility 13 32912613
2020 Upregulation of HLA-F expression by BK polyomavirus infection induces immune recognition by KIR3DS1-positive natural killer cells. Kidney international 11 33359499
2014 Infection of human amniotic and endothelial cells by Japanese encephalitis virus: Increased expression of HLA-F. Virology 11 25461528
2022 Long non-coding RNA HLA-F antisense RNA 1 inhibits the maturation of microRNA-613 in polycystic ovary syndrome to promote ovarian granulosa cell proliferation and inhibit cell apoptosis. Bioengineered 10 35603775
2021 High-throughput genotyping of HLA-G, HLA-F, MICA, and MICB and analysis of frequency distributions in healthy blood donors from Catalonia. HLA 10 33599111
2019 HLA-F Allele-Specific Peptide Restriction Represents an Exceptional Proteomic Footprint. International journal of molecular sciences 10 31717259
2004 Identification of a novel HLA-F allele - HLA-F*010102. Tissue antigens 10 14705989
2011 Promoter polymorphisms of the HLA-G gene, but not the HLA-E and HLA-F genes, is associated with non-segmental vitiligo patients in the Korean population. Archives of dermatological research 9 21847675
2023 HLA-F transcriptional and protein differential expression according to its genetic polymorphisms. HLA 8 37166140
2018 Human HLA‑F adjacent transcript 10 promotes the formation of cancer initiating cells and cisplatin resistance in bladder cancer. Molecular medicine reports 8 29749526
2014 HLA-F polymorphisms in a Euro-Brazilian population from Southern Brazil. Tissue antigens 8 25413105
2025 HLA-F regulates the proliferation of trophoblast via PKM2-dependent glycolysis in the pathogenesis of preeclampsia. Molecular medicine (Cambridge, Mass.) 6 40251569
2023 HLA-F and LILRB1 Genetic Polymorphisms Associated with Alloimmunisation in Sickle Cell Disease. International journal of molecular sciences 5 37686397
2022 Mobilisation of HLA-F on the surface of bronchial epithelial cells and platelets in asthmatic patients. HLA 5 35988034
2020 The Loss of HLA-F/KIR3DS1 Ligation Is Mediated by Hemoglobin Peptides. International journal of molecular sciences 4 33126487
2020 Evolution of HLA-F and its orthologues in primate species: a complex tale of conservation, diversification and inactivation. Immunogenetics 4 33184728
1996 A new highly polymorphic marker in the 5' untranslated region of HLA-F shows strong allelic association with haemochromatosis. Human genetics 4 8566959
2024 Diversity in the HLA-I Recognition of HLA-F Monoclonal Antibodies: HLA-F or HLA-Ib Monospecific, HLA-E or HLA-G Bispecific Antibodies with or without HLA-Ia Reactivity. Antibodies (Basel, Switzerland) 3 38390869
2024 Potentials as biomarker and therapeutic target of upregulated long non-coding RNA HLA-F antisense RNA 1 in hepatitis B virus-associated hepatocellular carcinoma. Virus genes 3 38568442
2022 Epigenome-Wide DNA Methylation Profiling of Normal Mucosa Reveals HLA-F Hypermethylation as a Biomarker Candidate for Serrated Polyposis Syndrome. The Journal of molecular diagnostics : JMD 3 35447336
2022 Sequence Variations Within HLA-G and HLA-F Genomic Segments at the Human Leukocyte Antigen Telomeric End Associated With Acute Graft-Versus-Host Disease in Unrelated Bone Marrow Transplantation. Frontiers in immunology 3 35935961
2021 LncRNA HLA-F-AS1 Enhances the Migration, Invasion and Apoptosis of Glioblastoma Cells by Targeting lncRNA MEG3. Cancer management and research 3 34934358
2021 DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B. Chinese journal of integrative medicine 2 33420581
2021 Human leukocyte antigen (HLA)-F and -G gene polymorphisms and haplotypes are associated with malaria susceptibility in the Beninese Toffin children. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 2 33781967
2026 HLA-F: A Non-Classical Gene With Growing Interest. HLA 1 41537416
2025 Association of HLA-Ib (HLA-G, HLA-E and HLA-F) with spontaneous HBV clearance. Infectious diseases (London, England) 1 40184242
2025 Investigations of HLA-F and HLA-G 3'UTR Polymorphisms in Preeclampsia and Fetal Growth Restriction Indicate a Possible Role of HLA-F-HLA-G Haplotypes and Diplotypes. HLA 1 40603242
2025 Emerging roles of natural killer cell ligands-HLA-E, HLA-F, HLA-G, MICA, and MICB-in in vitro fertilization outcomes. Frontiers in genetics 1 41321564
2024 Effect modification between HLA-F and CD56 markers reveals differences in survival for triple-negative breast cancer patients. Human immunology 1 39405828
2023 The novel HLA-F*01:16 and HLA-F*01:17 alleles identified in hematopoietic cell donors. HLA 1 38073430

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