Affinage

HLA-F

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

Length
346 aa
Mass
39.1 kDa
Annotated
2026-04-28
87 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-F is a non-classical MHC class Ib molecule that functions as a versatile immune regulator, serving both as a ligand for innate immune receptors on NK cells and as an unconventional peptide presenter on activated cells. Structurally, HLA-F forms a peptide-free open conformer associated with beta-2-microglobulin, TAP, and calreticulin in the endoplasmic reticulum; its surface mobilization upon cellular activation depends on cytoplasmic tail motifs that engage COPII and 14-3-3 trafficking machinery rather than on conventional peptide loading (PMID:10605026, PMID:16709803, PMID:20865824). At the cell surface, HLA-F open conformers serve as high-affinity ligands for the activating NK receptor KIR3DS1 and the inhibitory receptors ILT2, ILT4, KIR3DL2, and KIR2DS4, thereby triggering NK cell degranulation and cytokine production during viral infections including HIV, HCV, and BKV (PMID:27455421, PMID:11169396, PMID:24018270, PMID:30031767). When peptide-loaded, HLA-F presents non-canonically long peptides (8–24 residues) lacking a classical N-terminal anchor, with allele-specific repertoires and C-terminal lysine preference; peptide occupancy abolishes KIR3DS1 recognition, providing a molecular switch between activating and tolerogenic signaling (PMID:30941482, PMID:31717259, PMID:33126487).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1990 High

    Cloning of HLA-F revealed it encodes a structurally divergent MHC class I molecule with non-conservative substitutions in antigen-binding residues and a truncated cytoplasmic tail, establishing it as a non-classical class Ib gene with a predicted novel peptide-binding repertoire.

    Evidence DNA sequencing, protein sequence comparison, cDNA cloning and transfection in B cell lines

    PMID:1688605 PMID:1707659

    Open questions at the time
    • No protein-level confirmation of peptide binding at this stage
    • Biological function completely unknown
    • Receptor partners unidentified
  2. 2000 High

    Biochemical characterization established that HLA-F is predominantly an intracellular, peptide-free beta-2-microglobulin heterodimer associated with TAP and calreticulin, and identified ILT2 and ILT4 as direct receptor partners, redefining HLA-F as an open-conformer ligand for inhibitory leukocyte receptors.

    Evidence Recombinant protein refolding, SPR binding, immunoprecipitation, tetramers, thermostability assays, endoglycosidase-H analysis

    PMID:10605026 PMID:11169396

    Open questions at the time
    • Activating receptor partners unknown
    • Mechanism of ER retention vs. surface mobilization undefined
    • Whether HLA-F ever presents peptide in vivo unresolved
  3. 2000 Medium

    Dissection of HLA-F transcriptional regulation revealed NF-κB-, IFN-γ/ISRE-, and CIITA-dependent induction, placing HLA-F under both inflammatory and adaptive immune transcriptional control distinct from HLA-G.

    Evidence Promoter sequence analysis and transactivation assays

    PMID:11137213

    Open questions at the time
    • In vivo confirmation of each transcription factor's contribution lacking
    • Post-transcriptional regulation not addressed
    • Cell-type specificity of transcriptional control unexplored
  4. 2003 High

    Demonstration that HLA-F surface expression is TAP-independent and partially tapasin-independent resolved the question of how a peptide-free molecule reaches the surface, distinguishing HLA-F trafficking from classical MHC-I.

    Evidence Flow cytometry and endoglycosidase-H treatment in TAP- and tapasin-deficient cell lines

    PMID:14607927

    Open questions at the time
    • Positive trafficking signals not yet identified
    • Whether surface HLA-F carries any peptide cargo unresolved
  5. 2006 High

    Identification of cytoplasmic tail motifs (C-terminal valine for COPII, RxR for 14-3-3) as essential for HLA-F ER export provided a molecular explanation for its predominantly intracellular retention and activation-dependent surface mobilization.

    Evidence Tail deletion/point mutants, COPII and 14-3-3 interaction assays, surface expression analysis

    PMID:16709803

    Open questions at the time
    • Upstream signal linking cell activation to tail-dependent export unknown
    • Whether 14-3-3 binding is phosphorylation-regulated not tested
  6. 2010 High

    Systematic analysis across lymphocyte subsets showed that all resting lymphocytes store intracellular HLA-F and mobilize it to the surface upon activation — except regulatory T cells — establishing HLA-F surface display as a universal activation marker and defining its peptide-free open conformer as the predominant surface species that interacts with classical MHC-I open conformers.

    Evidence Flow cytometry and Western blot across B, T, NK, monocyte subsets; TAP/tapasin-deficient donor PBMCs; co-IP, SPR, and tetramer colocalization

    PMID:20483783 PMID:20865824

    Open questions at the time
    • Functional consequence of HLA-F–MHC-I open conformer interaction on signaling unknown
    • Treg-specific suppression mechanism undefined
  7. 2013 High

    Identification of KIR3DL2 and KIR2DS4 as additional receptors for HLA-F open conformers, together with a TAP-independent cross-presentation pathway mediated by HLA-F and MHC-I open conformers, expanded the functional repertoire from inhibitory signaling to both activating and antigen-presenting roles.

    Evidence SPR, biochemical pull-down, functional NK assays; cross-presentation assays with lysosomal inhibitors and MHC-I allotype blocking

    PMID:23851683 PMID:24018270

    Open questions at the time
    • Structural basis of KIR recognition of open conformers undefined
    • Cross-presentation pathway's in vivo relevance unestablished
    • Whether HLA-F itself cross-presents peptide or serves as co-receptor unclear
  8. 2016 High

    A comprehensive screen identified HLA-F open conformers as high-affinity ligands for the activating receptor KIR3DS1, establishing the HLA-F/KIR3DS1 axis as a major activating pathway for NK cell degranulation and antiviral cytokine production.

    Evidence Screening 100 HLA class I proteins, SPR, primary NK cell functional assays, HIV replication inhibition, HLA-null cell line blocking experiments

    PMID:27455421 PMID:27649529 PMID:29743316

    Open questions at the time
    • Crystal structure of HLA-F/KIR3DS1 complex not solved
    • Whether KIR3DS1 distinguishes among HLA-F alleles unknown
  9. 2019 High

    Mass spectrometry-based peptidome characterization of HLA-F revealed presentation of unconventionally long peptides (8–24 residues) without N-terminal anchoring but with C-terminal lysine preference, and showed complete allele-specific peptide repertoire divergence, defining a non-canonical antigen presentation mode.

    Evidence Soluble HLA technology, LC-MS peptidome from reconstituted HLA-F*01:01, *01:03, *01:04 complexes

    PMID:30941482 PMID:31717259

    Open questions at the time
    • In vivo T cell recognition of HLA-F-presented peptides undemonstrated
    • Structural basis of long-peptide accommodation unknown
    • Whether peptide-loaded HLA-F engages any receptor besides KIRs untested
  10. 2020 High

    Biochemical reconstitution showed that peptide loading onto HLA-F open conformers abolishes KIR3DS1 binding, establishing a molecular switch: peptide-free HLA-F activates NK cells via KIR3DS1 while peptide-loaded HLA-F does not, and HIV-driven enrichment of hemoglobin-derived peptides on HLA-F provides a viral immune evasion mechanism.

    Evidence Acid elution to generate open conformers, KIR3DS1 binding assay, MS proteomics of HIV-infected CD4+ T cells, peptide fraction loading and receptor recognition assay

    PMID:33126487

    Open questions at the time
    • How HIV promotes hemoglobin peptide loading specifically onto HLA-F is unknown
    • Whether other viruses exploit the same evasion mechanism untested
  11. 2018 Medium

    Discovery of a progesterone-responsive distal enhancer with an ancient polymorphism creating a GATA2 binding site that loops to the HLA-F promoter revealed tissue-specific endometrial regulation, connecting HLA-F to reproductive immunology and implantation.

    Evidence GTEx replication, reporter assay, chromatin looping analysis, progesterone treatment of decidual stromal cells

    PMID:30245028

    Open questions at the time
    • Functional consequence of enhanced HLA-F expression during implantation for NK cell tolerance unknown
    • Whether this enhancer operates in trophoblasts themselves untested
  12. 2021 Medium

    An unexpected non-immune function was established: HLA-F promotes glioma and trophoblast cell proliferation via metabolic reprogramming through stabilization of glycolytic enzymes HK2 and PKM2 respectively, with epistatic rescue upon enzyme silencing.

    Evidence Overexpression/knockdown, glycolysis measurements, xenograft models, ChIP-seq for PKM promoter binding, siRNA epistasis

    PMID:33867844 PMID:40251569

    Open questions at the time
    • How an MHC-I molecule directly regulates glycolytic enzyme expression/stability is mechanistically unexplained
    • Whether metabolic effects occur in immune cell contexts untested
    • Independent replication needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of HLA-F open conformer recognition by KIR3DS1, the mechanism by which HLA-F regulates glycolytic enzymes, whether peptide-loaded HLA-F engages adaptive T cell receptors in vivo, and how the switch between open conformer and peptide-loaded states is regulated during inflammation.
  • No crystal structure of HLA-F/KIR3DS1 complex
  • No TCR recognition of HLA-F-peptide complexes demonstrated
  • Molecular mechanism linking HLA-F to HK2/PKM2 stabilization uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-1430728 Metabolism 2 R-HSA-1474165 Reproduction 2
Partners
B2MHK2ILT2ILT4KIR2DS4KIR3DL2KIR3DS1PKM2
Complex memberships
MHC class I peptide-loading complex (TAP/calreticulin)

Evidence

Reading pass · 26 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 compared to classical HLA molecules, and five of ten conserved antigen-binding residues are altered (three non-conservatively), suggesting a divergent peptide-binding function. DNA sequencing and protein sequence analysis The Journal of experimental medicine High 1688605
1990 HLA-F protein, though intracellularly expressed after transfection into a B cell line, has a unique tissue distribution pattern (expressed in B cell lines, peripheral blood lymphocytes, absent from T cell lines and fibroblasts), and its transcript lacks exon 7 due to an altered acceptor splice site, resulting in a shorter cytoplasmic tail. Northern blot, cDNA cloning, transfection, Western blot International immunology High 1707659
2000 HLA-F heavy chain can be refolded with beta-2-microglobulin to form a stable complex; native HLA-F is predominantly intracellular and TAP-associated; HLA-F tetramers bind directly to ILT2 (LIR1) and ILT4 (LIR2) inhibitory receptors on monocytes and B cells, as confirmed by surface plasmon resonance. Recombinant protein refolding, monoclonal antibody production, immunoprecipitation, HLA-F tetramers, surface plasmon resonance, cell transfection European journal of immunology High 11169396
2000 HLA-F is expressed as a beta-2-microglobulin-associated 42-kDa empty heterodimer devoid of peptide; it is predominantly intracellular with immature oligosaccharide, associates with TAP and calreticulin, and IFN-gamma upregulates HLA-F mRNA and protein but does not induce cell surface expression. Immunoprecipitation, thermostability assays, endoglycosidase-H analysis, cell surface immunoprecipitation, Western blot Journal of immunology High 10605026
2000 HLA-F transcription is regulated by NF-kappaB (via the kappaB1 site of enhancer A), responds to IFN-gamma through the ISRE, and is inducible by CIITA through the SXY regulatory module, distinguishing its regulation from HLA-G. Promoter sequence analysis, transactivation assays Human immunology Medium 11137213
2003 HLA-F surface expression on B lymphoblastoid and monocyte cell lines is partially independent from tapasin and completely independent from TAP, in contrast to classical MHC class I molecules; an Endo H-sensitive surface form is tapasin-independent while an Endo H-resistant form is tapasin-dependent. Immunoprecipitation, endoglycosidase-H treatment, flow cytometry, genetic cell lines deficient in TAP or tapasin Journal of immunology High 14607927
2006 HLA-F export from the endoplasmic reticulum depends entirely on its cytoplasmic tail: a C-terminal valine residue interacts with COPII for ER export, and an RxR motif binds 14-3-3 proteins for anterograde transport; classical class I molecules lacking their cytoplasmic tail are still surface expressed, while HLA-F is not. Cytoplasmic tail deletion and point mutation constructs, COPII interaction assay, 14-3-3 protein binding assay, surface expression analysis Journal of immunology High 16709803
2010 HLA-F is expressed intracellularly in all resting lymphocytes (B, T, NK, monocytes) without surface expression; upon activation of any lymphocyte subtype, surface HLA-F is induced. This surface upregulation occurs even in TAP- and tapasin-deficient individuals, though with altered kinetics. CD4+CD25+ Tregs do not upregulate surface HLA-F upon activation unlike CD4+CD25- T cells. Western blot, flow cytometry, activation of diverse lymphocyte subpopulations, analysis of genetically TAP/tapasin-deficient donor PBMCs European journal of immunology High 20865824
2010 HLA-F is expressed at the cell surface independently of bound peptide (as an open conformer), and physically interacts with MHC class I heavy chains only when the latter are in the open conformer (peptide-free) form; this interaction was demonstrated by co-immunoprecipitation, surface plasmon resonance, and tetramer/MHC-I HC colocalization on the cell surface. Direct peptide-binding analysis of native HLA-F, co-immunoprecipitation, surface plasmon resonance, tetramer staining, cell surface colocalization Journal of immunology High 20483783
2013 HLA-F expressed as a peptide-free open conformer physically and functionally interacts with the NK cell inhibitory receptor KIR3DL2 and activating receptor KIR2DS4; classical MHC-I open conformers also serve as ligands for these KIRs, defining a new category of KIR-MHC interactions centered on the inflammatory response. Surface plasmon resonance, biochemical pull-down from cell lines, functional NK cell assays Journal of immunology High 24018270
2013 HLA-F and MHC-I open conformers on activated lymphocytes and monocytes mediate a cross-presentation pathway for exogenous antigens that is independent of TAP and tapasin, sensitive to lysosomal enzyme inhibitors, and dependent on MHC-I allotype-specific epitope recognition for antigen uptake. In vitro cross-presentation assays, TAP/tapasin inhibition, lysosomal enzyme inhibitors, MHC-I allotype-specific blocking Journal of immunology Medium 23851683
2016 HLA-F open conformers (peptide-free) are high-affinity ligands for the activating NK cell receptor KIR3DS1; activation of CD4+ T cells triggers surface expression of HLA-F, enabling KIR3DS1+ NK cell activation (degranulation, antiviral cytokine production); HIV-1 infection upregulates HLA-F mRNA but decreases KIR3DS1 binding, suggesting an immune evasion mechanism. Screening of 100 HLA class I proteins, biochemical binding assays, primary NK cell functional assays (degranulation, cytokine production), HIV-1 replication inhibition assay, flow cytometry Nature immunology High 27455421
2016 KIR3DS1 but not KIR3DL1 physically binds HLA-F and other MHC-I open conformers, as measured by surface plasmon resonance; this was corroborated by biochemical pull-down and heterodimerization experiments with recombinant proteins; HLA-F ligation of KIR3DS1 triggers granule exocytosis in activated NK cells. Surface plasmon resonance, biochemical pull-down, recombinant protein heterodimerization, granule exocytosis assay PloS one High 27649529
2014 HLA-F gene and protein expression are induced in JEV-infected human amniotic and endothelial cells via NFκB activation; shRNA knockdown of the p65 NFκB subunit blocks JEV-mediated HLA-F induction; TNF-alpha-driven HLA-F induction is also NFκB-dependent, and HLA-F enhancer A elements mediate NFκB-driven transactivation in reporter assays. RT-PCR, Western blot, shRNA knockdown of NFκB p65, luciferase reporter assay with HLA-F enhancer A elements, TNF-alpha stimulation Virology Medium 25461528
2018 HLA-F is upregulated on HCV-infected cells; interactions between KIR3DS1 on NK cells and HLA-F on HCV-infected cells contribute to NK cell-mediated control of HCV replication in cell culture and humanized mouse liver models. Cell culture model of HCV infection, humanized mouse liver model, primary liver biopsy analysis, KIR3DS1/HLA-F blocking experiments Gastroenterology Medium 30031767
2019 HLA-F*01:01 presents peptides with non-canonical features: no defined N-terminal anchor, preferred length of 16 residues, and nearly all source proteins interact with HIV proteins; stable peptide-HLA-F complexes could be reconstituted from naturally presented peptides. Soluble HLA technology, LC-MS peptide elution and sequencing from stable pHLA-F*01:01 complexes Immunogenetics High 30941482
2019 HLA-F allele-specific peptide selection differs completely among F*01:01, F*01:03, and F*01:04 despite polymorphisms outside peptide-binding pockets; all peptides are 8–24 amino acids, not N-terminally anchored, preferably C-terminally anchored by Lys; no proteomic overlap in peptide source proteins between allelic variants. Soluble HLA technology from K562 cells, LC-MS peptidome and proteome analysis, structural comparison of HLA-F allelic variants International journal of molecular sciences High 31717259
2020 Peptide-bound HLA-F complexes do not bind soluble KIR3DS1; acid elution of peptides generates HLA-F open conformers that bind KIR3DS1; hemoglobin-derived peptides are dominant in HLA-F allelic peptide repertoires in CD4+ T cells post-HIV infection, and loading of hemoglobin peptide fractions onto HLA-F open conformers significantly diminishes KIR3DS1 receptor recognition, providing a molecular mechanism for HIV immune escape. Soluble HLA technology, acid elution, KIR3DS1 binding assay, MS proteome analysis of CD4+/HIV+ vs CD4+/HIV- cells, peptide binding and receptor recognition assay International journal of molecular sciences High 33126487
2019 HLA-F on HIV-infected CD4+ T cells activates KIR3DS1+ NK cells (CCL4, IFN-gamma, CD107a), and blocking the HLA-F/KIR3DS1 interaction with KIR3DS1-Fc chimeric protein or anti-HLA-F antibody reduces the frequency of activated KIR3DS1+ NK cells. Co-culture of HIV-infected CD4+ T cells with primary NK cells, intracellular cytokine staining, degranulation assay, blocking with KIR3DS1-Fc chimera and anti-HLA-F mAb, exclusive gating strategies Journal of virology High 31270222
2018 HLA-F surface expression on the HLA-null cell line 721.221 activates primary KIR3DS1+ NK cells for CCL4, IFN-gamma, and CD107a secretion; blocking HLA-F on 721.221 cells with KIR3DS1-Fc chimeric protein or anti-HLA-F antibody reduces the frequency of activated KIR3DS1+ NK cells. Coculture of HLA-null 721.221 cells expressing HLA-F with primary NK cells, intracellular cytokine staining, degranulation assay, blocking experiments Journal of immunology High 29743316
2020 BK polyomavirus infection significantly increases surface expression of HLA-F on kidney tubular cells, enhancing KIR3DS1 binding and activating primary KIR3DS1+ NK cells, providing a mechanism for NK cell-mediated control of BKV infection. In vitro BKV infection model, flow cytometry of surface HLA-F, KIR3DS1 binding assay, primary NK cell activation assay, kidney biopsy analysis Kidney international Medium 33359499
2021 HLA-F promotes proliferation of glioma cells via HK2-dependent glycolysis: forced HLA-F expression increased HK2 protein stabilization and aerobic glycolysis phenotype; silencing HK2 reduced HLA-F-mediated glycolysis and cell proliferation. Forced HLA-F overexpression, HK2 shRNA knockdown, in vitro proliferation assays, glycolysis measurements, in vivo xenograft in immunodeficient Rag2 mice with anti-HLA-F antibody treatment International journal of biological sciences Medium 33867844
2025 HLA-F regulates trophoblast proliferation via PKM2-dependent glycolysis: HLA-F overexpression promotes PKM2 protein expression and enzymatic activity, enhancing glycolysis; HLA-F binds the PKM promoter (shown by ChIP-seq) and reduces lactylation at PKM2 K305, increasing enzyme activity; PKM2 siRNA silencing abolishes HLA-F-mediated proliferation. ChIP-seq, 4D label-free quantitative proteomics, siRNA knockdown, CCK8/MTT/colony assay, Mini-PDX model, immunofluorescence, enzymatic activity assays Molecular medicine Medium 40251569
2022 HLA-F is mobilized to the surface of bronchial epithelial cells and platelets in an inflammatory/asthmatic context without changes at the transcriptional level, indicating surface expression is a ubiquitous post-transcriptional process in activated non-immune cells as well. Flow cytometry of surface HLA-F, RT-PCR for transcription, comparison of healthy vs. asthmatic donors, chemical activation experiments HLA Medium 35988034
2018 An ancient G/A polymorphism at SNP rs2523393 creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter, upregulating HLA-F expression in the endometrium during the window of implantation and in decidual stromal cells treated with progesterone. GTEx replication, reporter assay, chromatin looping analysis (3D genome), GATA2 binding site identification, progesterone treatment of decidual stromal cells American journal of human genetics Medium 30245028
2023 HLA-F overexpression in Jar trophoblast cells promotes cell proliferation, invasion, and migration; in NK-92MI cells, HLA-F overexpression increases secretion of immunoregulation cytokines (CSF1, CCL22) and promotes adaptive NKG2C+ NK cell transformation. HLA-F lentiviral overexpression, CCK-8/proliferation assay, invasion/migration assay, cytokine measurement, flow cytometry of NK cell phenotypes 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 199 1688605
2016 Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. Nature immunology 190 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) 123 28185362
2013 HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors. Journal of immunology (Baltimore, Md. : 1950) 118 24018270
1996 Identification of seven new human MHC class I region genes around the HLA-F locus. Immunogenetics 118 8662070
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 92 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) 87 10605026
2006 Selective export of HLA-F by its cytoplasmic tail. Journal of immunology (Baltimore, Md. : 1950) 72 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) 68 14607927
2010 HLA-F complex without peptide binds to MHC class I protein in the open conformer form. Journal of immunology (Baltimore, Md. : 1950) 66 20483783
1993 Characterization of the rhesus macaque (Macaca mulatta) equivalent of HLA-F. Immunogenetics 52 8482576
2013 HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway. Journal of immunology (Baltimore, Md. : 1950) 51 23851683
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
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
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 44 22544725
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 40 30031767
2019 Correlation of alteration of HLA-F expression and clinical characterization in 593 brain glioma samples. Journal of neuroinflammation 38 30755240
2016 Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies HLA-F and TAP2 as Fecundability-Associated Genes. PLoS genetics 38 27447835
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
2019 A role for both HLA-F and HLA-G in reproduction and during pregnancy? Human immunology 29 31558330
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
2018 An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F. American journal of human genetics 28 30245028
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
2023 Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia. Frontiers in immunology 24 37854606
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) 23 35689445
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
2016 HLA-F coding and regulatory segments variability determined by massively parallel sequencing procedures in a Brazilian population sample. Human immunology 22 27448841
2022 HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation. Cancer genomics & proteomics 21 35181585
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
2021 Targeting HLA-F suppresses the proliferation of glioma cells via a reduction in hexokinase 2-dependent glycolysis. International journal of biological sciences 19 33867844
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
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
2013 Characterization of HLA-F polymorphism in four distinct populations in Mainland China. International journal of immunogenetics 17 23551590
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
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
2020 Upregulation of HLA-F expression by BK polyomavirus infection induces immune recognition by KIR3DS1-positive natural killer cells. Kidney international 10 33359499
2014 Infection of human amniotic and endothelial cells by Japanese encephalitis virus: Increased expression of HLA-F. Virology 10 25461528
2004 Identification of a novel HLA-F allele - HLA-F*010102. Tissue antigens 10 14705989
2021 High-throughput genotyping of HLA-G, HLA-F, MICA, and MICB and analysis of frequency distributions in healthy blood donors from Catalonia. HLA 9 33599111
2019 HLA-F Allele-Specific Peptide Restriction Represents an Exceptional Proteomic Footprint. International journal of molecular sciences 9 31717259
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.) 5 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 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
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) 2 38390869
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
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
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
2026 HLA-F: A Non-Classical Gene With Growing Interest. HLA 0 41537416
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 0 41321564