Affinage

HLA-C

HLA class I histocompatibility antigen, C alpha chain · UniProt P10321

Length
366 aa
Mass
40.6 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-C is a classical MHC class I molecule that presents peptides to cytotoxic T cells and serves as the dominant ligand for the KIR family of NK cell receptors, functioning as a transplantation antigen and CTL restriction element comparable to HLA-A and -B (PMID:2840670, PMID:2246509). Its allotype-defining C1/C2 dimorphism at positions 77/80 partitions NK recognition: distinct residue pairs determine which inhibitory NK subset is protected (PMID:8265660), with inhibitory p58/KIR2DL receptors binding HLA-C in a peptide-influenced manner while homologous activating p50 receptors bind weakly or not at all—differences dictated by the receptor transmembrane/cytoplasmic domains (PMID:9826699, PMID:9378975). Crystallographic and functional analyses show that closely related KIRs (KIR2DL2 vs. KIR2DL3) adopt different docking geometries on HLA-C1 and differ in allotype recognition (PMID:33846289), that the activating KIR2DS4 reads specific bound peptides including conserved bacterial motifs presented by HLA-C*05:01 (PMID:31138701), and that the C1/C2 polymorphism shapes the C-terminal peptide repertoire to influence both KIR and TCR discrimination of identical epitopes (PMID:2246509, PMID:35587797). A defining feature of HLA-C is its characteristically low surface expression, governed by multiple layers: accelerated mRNA degradation directed by a 3′ UTR element (PMID:7760000), post-transcriptional suppression via miR-148a binding to a 3′ UTR polymorphism whose strength causally tunes HIV control (PMID:21499264, PMID:24248364), an Oct1-binding promoter SNP that modulates transcription (PMID:27817866), and an NK cell-specific promoter generating untranslatable alternative transcripts during NK maturation (PMID:29329284). HLA-C is a target of viral immune evasion: HIV-1 Vpu selectively downregulates HLA-C through defined transmembrane residue contacts to escape CTL killing and modulate NK sensing (PMID:27173934, PMID:30180214, PMID:28704647), while HSV-2 ICP47 downregulates HLA-C via a cytoplasmic tail motif to redirect NK killing of infected dendritic cells (PMID:23555244). At the maternal–fetal interface, HLA-C is expressed on extravillous trophoblast in association with β2-microglobulin and is upregulated by IFN-γ (PMID:10833373), with NLRP2 suppressing its expression through inhibition of NF-κB signaling (PMID:28340094).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1988 High

    Established that HLA-C is a bona fide immunological MHC class I molecule rather than a vestigial locus, settling whether it could serve antigen-presentation functions like HLA-A and -B.

    Evidence HLA-Cw3 transgenic C57BL/6 mice tested in skin graft rejection and viral CTL restriction assays

    PMID:2840670

    Open questions at the time
    • Did not address peptide repertoire or why HLA-C surface levels are low
    • Single allele tested
  2. 1990 Medium

    Confirmed in a human system that HLA-C functions as an alloantigen capable of priming CTL, reinforcing its role as a class I restriction element.

    Evidence CTL clone cytotoxicity using transfected and primary cells with monomorphic class I antibody blocking

    PMID:2246509

    Open questions at the time
    • Single lab
    • Did not define molecular basis of recognition
  3. 1993 High

    Defined the C1/C2 dimorphism at positions 77/80 as the determinant of which NK cell subset HLA-C inhibits, founding the HLA-C–NK recognition framework.

    Evidence Allele-specific transfection into class I-deleted lines with NK cytotoxicity readout

    PMID:8265660

    Open questions at the time
    • Receptor identity not molecularly resolved at the time
    • Did not explain inhibitory vs. activating distinction
  4. 1995 High

    Resolved why HLA-C surface expression is low, showing the cause is post-transcriptional mRNA instability rather than heavy chain or peptide-binding defects.

    Evidence mRNA half-life measurements, B7/Cw3 chimeric gene transfection, β2m competition assays

    PMID:7760000

    Open questions at the time
    • Did not identify the trans-acting factor mediating 3′ UTR degradation
    • Polymorphic control not yet mapped
  5. 1997 Medium

    Demonstrated direct physical binding of inhibitory p58 KIRs to soluble HLA-C and a peptide dependence of that interaction, establishing the biochemical basis of KIR/HLA-C recognition.

    Evidence Native gel shift with recombinant soluble KIR and HLA-Cw3/Cw6, peptide competition

    PMID:9378975

    Open questions at the time
    • Single lab
    • Did not explain why activating KIRs fail to bind
  6. 1998 High

    Showed that inhibitory versus activating function in KIR/HLA-C pairs is set by the transmembrane/cytoplasmic domains, not ligand affinity, since activating p50 receptors bind HLA-C poorly.

    Evidence Kinetic binding assays comparing inhibitory NKAT2 and activating p50 receptors to HLA-Cw7

    PMID:9826699

    Open questions at the time
    • Did not address peptide-specific activating recognition
    • Structural docking not defined
  7. 2000 High

    Established that HLA-C is expressed on extravillous trophoblast as a β2m-associated, IFN-γ-responsive molecule, placing it at the maternal–fetal interface.

    Evidence cDNA sequencing, biochemistry, flow cytometry, IHC, and IFN-γ stimulation of trophoblast

    PMID:10833373

    Open questions at the time
    • Functional consequence for placentation not tested here
    • Regulatory mechanism of trophoblast expression unknown
  8. 2011 High

    Identified miR-148a binding to a 3′ UTR polymorphism as a molecular mechanism setting allele-specific HLA-C surface levels and linked expression level to HIV control.

    Evidence Allele-specific 3′ UTR reporter and miRNA binding assays with surface expression and HIV association

    PMID:21499264

    Open questions at the time
    • Did not establish causality independent of linked HLA loci
    • Other 3′ UTR regulators not excluded
  9. 2012 Medium

    Provided in vivo evidence of functional activating HLA-C2–KIR2DS1 engagement by showing HLA-C2 abrogates KIR2DS1-mediated protection against AML relapse.

    Evidence Retrospective HSCT cohort with donor KIR and donor/recipient HLA-C genotyping

    PMID:22931314

    Open questions at the time
    • Single retrospective cohort
    • Direct biochemical KIR2DS1/C2 interaction not measured here
  10. 2013 High

    Demonstrated causal control of HIV outcome by HLA-C expression level via a MIR148A indel acting only when the 3′ UTR binding site is intact, isolating HLA-C dosage as the effector.

    Evidence Genetic epistasis between MIR148A indel and HLA-C 3′ UTR genotype across cohorts

    PMID:24248364

    Open questions at the time
    • Mechanism by which higher HLA-C improves HIV control not fully resolved
    • Does not address NK vs. CTL contribution
  11. 2013 High

    Revealed selective viral targeting of HLA-C by HSV-2 ICP47 via an HLA-C cytoplasmic tail motif, redirecting NK killing toward infected dendritic cells.

    Evidence DC infection, ICP47 mutagenesis/overexpression, HLA-C tail motif mapping, NK cytotoxicity

    PMID:23555244

    Open questions at the time
    • Mechanism of tail-motif-dependent downregulation not defined
    • In vivo relevance not established
  12. 2016 High

    Mapped an Oct1-binding promoter SNP as a major transcriptional determinant of HLA-C surface levels, adding a transcriptional layer to expression control.

    Evidence impeQTL mapping, qPCR, flow cytometry, EMSA, and luciferase reporter assays

    PMID:27817866

    Open questions at the time
    • Interplay with 3′ UTR/miR-148a control not quantified
    • Cell-type specificity of Oct1 effect not resolved
  13. 2016 High

    Identified HIV-1 Vpu as the mediator that selectively downregulates HLA-C in primary isolates to blunt CTL suppression, distinguishing HLA-C from HLA-A/-B in viral evasion.

    Evidence Primary HIV-1 clone infection, flow cytometry, CTL suppression, siRNA/Vpu mutant analysis

    PMID:27173934

    Open questions at the time
    • Molecular contact residues not yet defined at this stage
    • NK consequences not addressed
  14. 2017 High

    Defined the transmembrane residues mediating Vpu–HLA-C interaction and showed downregulation adapts to host HLA-C genotype during chronic infection.

    Evidence Site-directed mutagenesis of Vpu and HLA-C TM domains with viral quasispecies analysis across individuals

    PMID:30180214

    Open questions at the time
    • Structural model of the TM interaction absent
    • Trafficking pathway of downregulated HLA-C unclear
  15. 2017 Medium

    Showed NK cells sense the degree of HIV-1-mediated HLA-C loss, linking inhibitory KIR/HLA-C engagement to NK antiviral activity and licensing.

    Evidence Flow cytometry for HLA-C–KIR binding and NK antiviral assays across viral strains

    PMID:28704647

    Open questions at the time
    • Single lab
    • Mechanism of licensed-NK reduced activity not fully resolved
  16. 2017 Medium

    Implicated HLA-C free chains in HIV-1 infectivity, showing β2m-dependent Env association and a requirement for prior β2m assembly.

    Evidence Flow cytometry for β2m-free HLA-C, β2m-conditioned pseudovirus infectivity, Env co-IP

    PMID:28051183

    Open questions at the time
    • Single lab
    • Mechanism by which free chains enhance infectivity unresolved
  17. 2017 Medium

    Identified NLRP2 as a trophoblast suppressor of HLA-C expression acting through inhibition of NF-κB signaling, defining a placental regulatory axis.

    Evidence TALEN deletion and shRNA knockdown of NLRP2 in JEG3/primary EVT with NF-κB phosphorylation and HLA-C flow cytometry

    PMID:28340094

    Open questions at the time
    • Single lab
    • In vivo placental consequence not tested
  18. 2008 Medium

    Reported that virion-incorporated HLA-C associates with gp120 and enhances HIV-1 infectivity, proposing a non-immune role in viral entry.

    Evidence siRNA knockdown, cell fusion and pseudovirus infectivity, HLA-C/gp120 co-purification

    PMID:18673537

    Open questions at the time
    • Single lab
    • Mechanism of infectivity enhancement not defined
  19. 2018 Medium

    Uncovered an NK-specific HLA-C promoter producing untranslatable transcripts whose proportion drops during NK maturation, coupling expression control to NK education.

    Evidence NK-Pro identification, RT-PCR of alternative transcripts, luciferase reporters, maturation correlation

    PMID:29329284

    Open questions at the time
    • Single lab
    • Mechanism switching promoter usage during maturation unknown
  20. 2021 High

    Provided structural basis for differential HLA-C1 recognition by KIR2DL2 vs. KIR2DL3 and linked allotype-specific docking to functional NK inhibition involving KIR2DS2.

    Evidence X-ray crystallography of KIR2DL2/L3–HLA-C*07:02, mutagenesis, primary NK inhibition assays

    PMID:33846289

    Open questions at the time
    • Did not resolve activating KIR2DS2 structural mechanism
    • Peptide-dependence of geometry not fully mapped
  21. 2019 High

    Showed the activating KIR2DS4 recognizes specific peptides (p8-Trp) on HLA-C*05:01, including conserved bacterial motifs, defining peptide-specific NK activation.

    Evidence Peptide binding, KIR2DS4 tetramer binding, NK degranulation, allele-frequency correlation

    PMID:31138701

    Open questions at the time
    • In vivo antibacterial relevance not established
    • Restricted to HLA-C*05:01
  22. 2022 High

    Demonstrated that the C1/C2 dimorphism shapes C-terminal peptide preferences and modulates TCR discrimination of identical neoantigens, unifying NK and T cell relevance of the polymorphism.

    Evidence Structural analysis, immunopeptidomics, SPR for TCR affinity, T cell assays with C1/C2-matched allotypes

    PMID:35587797

    Open questions at the time
    • Generalization beyond KRAS-G12D neoantigen not tested
    • Does not address NK consequences of repertoire shifts

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple expression-control layers (3′ UTR/miR-148a, Oct1 promoter, NK-specific promoter, NLRP2/NF-κB) are integrated across cell types and how peptide repertoire jointly tunes NK and T cell recognition remains unresolved.
  • No integrated model combining transcriptional and post-transcriptional control
  • Cell-type-specific weighting of each mechanism unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 5 R-HSA-1643685 Disease 4
Partners
B2MKIR2DL2KIR2DL3KIR2DS1KIR2DS4VPU

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 HLA-C alleles are the dominant inhibitory ligands that protect target cells from lysis by NK1- and NK2-specific NK cells. Transfection of class I-deleted mutant cell lines with HLA-C alleles encoding Asn-77/Lys-80 (e.g., HLA-Cw4, -Cw5, -Cw6) inhibited lysis by NK1-specific NK cells, while alleles encoding Ser-77/Asn-80 (e.g., HLA-Cw1, -Cw7, -Cw13) protected targets from NK2-specific NK cells. The dimorphism at positions 77–80 of HLA-C determines which NK cell subset is inhibited. Transfection of HLA-C alleles into class I-deleted mutant cell lines followed by NK cell cytotoxicity assays Proceedings of the National Academy of Sciences of the United States of America High 8265660
1988 HLA-Cw3 expressed in transgenic C57BL/6 mice functions as a transplantation antigen (transgenic skin rapidly rejected by normal mice) and as a restriction element for cytotoxic T lymphocytes specific for influenza and Sendai virus, demonstrating immunological functions comparable to HLA-A and -B. Transgenic mouse model; skin graft rejection assay; CTL restriction assay with viral antigens Proceedings of the National Academy of Sciences of the United States of America High 2840670
1995 Low cell surface expression of HLA-C is caused primarily by faster degradation of HLA-C mRNA (not by intrinsic properties of the heavy chain protein), and the region determining low expression lies between the 3′ end of exon 3 and a site ~600 bases downstream of the translation stop codon in the 3′ UTR. HLA-C heavy chains associate with and dissociate from β2-microglobulin at rates comparable to HLA-A and -B, and increased β2m competition does not alter HLA-C surface expression. Chimeric B7/Cw3 proteins with the B7 peptide-binding groove can still have low surface expression, indicating peptide-binding inefficiency is not the primary cause. mRNA half-life measurement, chimeric gene transfection (HLA-B7/Cw3 and B7/Cw6), β2m competition assays, cell surface expression analysis The Journal of experimental medicine High 7760000
1998 The inhibitory p58 receptor NKAT2 binds HLA-Cw7 with rapid association and dissociation kinetics, whereas the homologous activating p50 receptors (clone 49 and clone 39) bind HLA-C only very weakly or not at all, demonstrating that the transmembrane/cytoplasmic domains—not the extracellular domains—determine functional (inhibitory vs. activating) differences in KIR binding to HLA-C. Direct binding assays comparing inhibitory and activating KIR receptors to HLA-Cw7; kinetic analysis of association/dissociation rates Proceedings of the National Academy of Sciences of the United States of America High 9826699
1997 Recombinant soluble p58 KIR molecules (KIR-K6 and KIR-K7) directly bind recombinant soluble HLA-Cw3 and HLA-Cw6, as shown by native gel shift assay. The activating p50 KAR-K1 binds neither HLA-C molecule. KIR binding to HLA-C is influenced by the antigenic peptide bound to the MHC molecule, and requires both Ig domains of p58. Native gel shift assay with recombinant soluble KIR and HLA-C proteins; peptide competition Journal of immunology (Baltimore, Md. : 1950) Medium 9378975
2000 HLA-C protein is expressed on the cell surface of normal extravillous trophoblast cells in association with β2-microglobulin; both paternal and maternal HLA-C alleles are transcribed and expressed. IFN-γ treatment upregulates HLA-C but not HLA-G surface expression on trophoblasts. HLA-C is expressed by all extravillous trophoblast subpopulations in vivo. cDNA sequencing of sorted trophoblast cells; biochemical analysis; flow cytometry with HLA-C-specific antibody; immunohistology; IFN-γ stimulation Placenta High 10833373
2011 A SNP within the 3′ UTR of HLA-C regulates binding of hsa-miR-148a to the HLA-C mRNA, resulting in post-transcriptional downregulation; alleles that bind miR-148a show relatively low surface expression while alleles that escape miR-148a binding show high surface expression. This mechanism underlies differential HLA-C cell surface expression and associates with HIV control. miRNA binding assays; allele-specific 3′ UTR reporter assays; flow cytometry for surface expression; association with HIV control Nature High 21499264
2013 A MIR148A insertion/deletion polymorphism affects miR-148a expression levels, which in turn modulates the degree of HLA-C downregulation and the level of HIV control—but only in individuals carrying an intact miR-148a binding site in the HLA-C 3′ UTR. This demonstrates a direct causal effect of HLA-C expression level on HIV control independent of other HLA loci. Genetic association of MIR148A indel with miR-148a expression, HLA-C surface levels, and HIV control; interaction analysis conditioned on HLA-C 3′ UTR genotype Proceedings of the National Academy of Sciences of the United States of America High 24248364
2016 A promoter SNP rs2395471 located in an Oct1 transcription factor consensus binding site ~800 bp upstream of the HLA-C transcription start site regulates HLA-C expression: the A allele has higher Oct1 binding affinity and higher promoter activity than the G allele, as shown by electrophoretic mobility shift assay (Oct1 binds both alleles) and luciferase reporter assay. This variant accounts for up to 36% of explained variation in HLA-C cell surface levels. Imputed expression QTL (impeQTL) mapping; quantitative PCR; flow cytometry; electrophoretic mobility shift assay (EMSA); luciferase reporter assay American journal of human genetics High 27817866
2016 HIV-1 Vpu mediates downregulation of HLA-C on infected cells, reducing HLA-C-restricted CTL suppression of viral replication in CD4+ cells. HLA-A and HLA-B are unaffected by Vpu. Most primary HIV-1 clones (including transmitted founder viruses) downregulate HLA-C via Vpu, in contrast to the laboratory-adapted NL4-3 strain. Primary HIV-1 clone infection assays; flow cytometry for HLA-C surface expression; CTL suppression assay; siRNA/Vpu mutant analysis Cell host & microbe High 27173934
2018 HIV-1 downregulation of HLA-C involves specific residues in the transmembrane region of Vpu (5 residues) and the transmembrane domain of HLA-C (4 residues) that determine Vpu–HLA-C interactions. HLA-C downregulation by Vpu adapts to host HLA genotype during chronic infection; individuals with higher HLA-C expression favor greater viral downregulation. Site-directed mutagenesis of Vpu and HLA-C transmembrane domains; replication-competent viral isolates from 19 individuals; viral quasispecies analysis PLoS pathogens High 30180214
2013 HSV-2 specifically downregulates HLA-C (but not HLA-A or HLA-B) on infected dendritic cells via the viral protein ICP47, rendering infected DCs susceptible to NK cell killing. A specific motif in the cytoplasmic tail of HLA-C is responsible for HSV-2-mediated HLA-C downregulation. Viral infection of DCs; flow cytometry; ICP47 mutagenesis/overexpression; NK cell cytotoxicity assay; identification of HLA-C cytoplasmic tail motif PLoS pathogens High 23555244
2017 HIV-1-mediated downmodulation of HLA-C reduces binding to inhibitory KIRs on NK cells. Despite this, HLA-C-licensed NK cells display reduced antiviral activity compared to unlicensed NK cells, potentially due to residual KIR/HLA-C interaction. NK cells can sense the degree of HLA-C downmodulation by HIV-1, with greater downmodulation correlating with increased NK antiviral activity. Flow cytometry for HLA-C–KIR binding; NK cell antiviral activity assays; comparison of HIV-1 strains with differential HLA-C downmodulation capacity Cell host & microbe Medium 28704647
2008 HLA-C (incorporated into HIV-1 virions) associates with envelope glycoprotein gp120 and enhances HIV-1 infectivity. Silencing HLA-C by siRNA reduces syncytia formation and pseudovirus infectivity. HLA-C co-purifies with gp120 from cells before and after fusion and is present in fusion complexes. siRNA knockdown of HLA-C; cell fusion assays; pseudovirus infectivity assays; co-purification of HLA-C with gp120 Retrovirology Medium 18673537
2017 HIV-1 specifically increases the amount of HLA-C free chains (not bound to β2-microglobulin) on the membrane of infected cells. The association between HIV-1 Env and HLA-C at the cell membrane requires β2m to occur. The enhanced infectivity conferred by HLA-C specifically involves HLA-C free-chain molecules that have been previously correctly assembled with β2m; pseudoviruses produced in the absence of β2m are less infectious. Flow cytometry for β2m-free HLA-C chains; pseudovirus infectivity assays in β2m-present vs. β2m-absent conditions; co-immunoprecipitation of Env with HLA-C Scientific reports Medium 28051183
2017 NLRP2 acts as a suppressor of HLA-C expression in trophoblasts: deletion of NLRP2 in JEG3 cells (trophoblast model) using TALEN technology caused a significant increase in constitutive HLA-C expression, and NLRP2 knockdown by lentiviral shRNA in JEG3 and primary EVT increased TNFα-induced NF-κB p65 phosphorylation. This indicates NLRP2 regulates HLA-C expression via suppression of NF-κB signaling. TALEN-mediated NLRP2 deletion; lentiviral shRNA knockdown; NF-κB phosphorylation assay; flow cytometry for HLA-C surface expression Biology of reproduction Medium 28340094
2018 An NK cell-specific HLA-C promoter (NK-Pro) drives expression of an array of alternative transcripts with varying exon content. Skipping of the first coding exon generates untranslatable HLA-C mRNAs; the proportion of untranslatable mRNA decreases as NK cells mature, correlating with increased HLA-C protein expression. A polymorphism in a key Ets-binding site of the NK-Pro generates HLA-C alleles that lack significant promoter activity, resulting in reduced HLA-C expression and increased NK functional activity. NK-specific promoter identification; RT-PCR for alternative transcripts; luciferase reporter assay for NK promoter activity; correlation of transcript ratios with NK maturation and HLA-C protein levels PLoS genetics Medium 29329284
2021 Crystal structures of KIR2DL2 and KIR2DL3 in complex with HLA-C*07:02 presenting a self-epitope reveal that KIR2DL2 adopts a different docking geometry atop HLA-C compared to KIR2DL3. Mutagenesis assays showed differences in HLA-C1 allotype recognition between KIR2DL2 and KIR2DL3. HLA-C1 allotypes differ markedly in their capacity to inhibit primary NK cell activation, and these functional differences involve KIR2DS2. X-ray crystallography; mutagenesis; primary NK cell inhibition assays Nature communications High 33846289
2019 The activating receptor KIR2DS4 has strong preference for peptides carrying Trp at position 8 (p8) of 9-mer peptides bound to HLA-C*05:01. A complex of HLA-C*05:01 with a p8-Trp peptide is sufficient to activate primary KIR2DS4+ NK cells independently of other activating receptors and NK cell licensing. A conserved bacterial RecA peptide motif presented by HLA-C*05:01 activates KIR2DS4+ NK cells from multiple human pathogens (Helicobacter, Chlamydia, Brucella, Campylobacter). Peptide binding assays; flow cytometry for NK cell degranulation; KIR2DS4 tetramer binding; worldwide allele frequency correlation analysis Proceedings of the National Academy of Sciences of the United States of America High 31138701
2022 The C1/C2 dimorphism at positions 77 and 80 of HLA-C impacts peptide presentation: Ser77 (C1) vs. Asn77 (C2) influences amino acid preference near the peptide C-terminus (pΩ and pΩ-1 positions), with C1 favoring small and C2 preferring large residues. KRAS-G12D neoantigen-specific TCRs discriminate between C1 and C2 allotypes presenting the same peptide, with weaker TCR affinity for KRAS-G12D-bound C2-HLA-C despite conserved TCR contacts. Structural analysis; immunopeptidomics; SPR (surface plasmon resonance) for TCR affinity; functional T cell assays; HLA-C allotypes differing only at C1/C2-defining residues eLife High 35587797
1990 HLA-C blank antigens (Cb-1 and Cb-2) are functionally expressed on the surface of peripheral blood lymphocytes (EBV-transformed B cells and PHA-induced T cells), can induce allogeneic CTL responses comparable to HLA-B, and are recognized in a class I-specific manner (blocked by anti-class I monomorphic mAb), indicating HLA-C can function as an alloantigen in vivo. CTL clone cytotoxicity assays using transfected Hmy2CIR cells and primary PBL; blocking with class I monomorphic mAb Journal of immunology (Baltimore, Md. : 1950) Medium 2246509
2012 Donor KIR2DS1-mediated prevention of AML relapse after allogeneic HSCT is HLA-C-dependent: protection was observed in donors with KIR2DS1 who were homozygous/heterozygous for HLA-C1, but not in donors homozygous for HLA-C2 (who are auto-licensed through KIR2DS1/C2 interaction). This establishes that HLA-C2 ligand engagement of KIR2DS1 in the donor abrogates the antileukemic effect, demonstrating functional HLA-C–KIR2DS1 interaction in vivo. Retrospective clinical cohort (n=1277 AML patients); donor KIR genotyping; donor/recipient HLA-C genotyping; statistical survival/relapse analysis The New England journal of medicine Medium 22931314

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. American journal of human genetics 468 16642438
1993 HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells. Proceedings of the National Academy of Sciences of the United States of America 404 8265660
2012 HLA-C-dependent prevention of leukemia relapse by donor activating KIR2DS1. The New England journal of medicine 360 22931314
2011 Differential microRNA regulation of HLA-C expression and its association with HIV control. Nature 275 21499264
2009 HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C. Nature genetics 241 19935663
2000 Localization of psoriasis-susceptibility locus PSORS1 to a 60-kb interval telomeric to HLA-C. American journal of human genetics 195 10801386
2000 Surface expression of HLA-C antigen by human extravillous trophoblast. Placenta 192 10833373
1992 Distinctive polymorphism at the HLA-C locus: implications for the expression of HLA-C. The Journal of experimental medicine 176 1383381
1995 Low HLA-C expression at cell surfaces correlates with increased turnover of heavy chain mRNA. The Journal of experimental medicine 165 7760000
1998 Differential binding to HLA-C of p50-activating and p58-inhibitory natural killer cell receptors. Proceedings of the National Academy of Sciences of the United States of America 147 9826699
2003 Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. The Journal of investigative dermatology 140 12648227
2011 Maternal KIR and fetal HLA-C: a fine balance. Journal of leukocyte biology 131 21873457
2016 HIV-1 Vpu Mediates HLA-C Downregulation. Cell host & microbe 120 27173934
2002 Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus. Human molecular genetics 105 11875053
2019 The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface. Frontiers in immunology 104 31921098
2001 Identification of a novel psoriasis susceptibility locus at 1p and evidence of epistasis between PSORS1 and candidate loci. Journal of medical genetics 101 11134234
1988 Immunological function of HLA-C antigens in HLA-Cw3 transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 101 2840670
2015 Polymorphic HLA-C Receptors Balance the Functional Characteristics of KIR Haplotypes. Journal of immunology (Baltimore, Md. : 1950) 100 26311903
1989 Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles. Immunogenetics 93 2714852
2008 Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome. Molecular immunology 91 18289678
2013 Genetic interplay between HLA-C and MIR148A in HIV control and Crohn disease. Proceedings of the National Academy of Sciences of the United States of America 90 24248364
2011 HLA-C as a mediator of natural killer and T-cell activation: spectator or key player? Immunology 85 21355865
2009 Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection. AIDS (London, England) 82 19050382
2000 HLA-C and guttate psoriasis. The British journal of dermatology 80 11122018
2017 Missing or altered self: human NK cell receptors that recognize HLA-C. Immunogenetics 78 28695291
2005 The major psoriasis susceptibility locus PSORS1 is not a risk factor for late-onset psoriasis. The Journal of investigative dermatology 73 15654960
2008 Fine mapping of the psoriasis susceptibility locus PSORS1 supports HLA-C as the susceptibility gene in the Han Chinese population. PLoS genetics 71 18369457
2003 Roles of HLA-B, HLA-C and HLA-DPA1 incompatibilities in the outcome of unrelated stem-cell transplantation. Tissue antigens 71 12956878
2019 Human NK cell receptor KIR2DS4 detects a conserved bacterial epitope presented by HLA-C. Proceedings of the National Academy of Sciences of the United States of America 69 31138701
2007 TNF polymorphisms in psoriasis: association of psoriatic arthritis with the promoter polymorphism TNF*-857 independent of the PSORS1 risk allele. Arthritis and rheumatism 67 17530646
2011 The emerging role of HLA-C in HIV-1 infection. Immunology 53 21896007
2005 HLA-C and killer cell immunoglobulin-like receptor genes in idiopathic bronchiectasis. American journal of respiratory and critical care medicine 51 16254274
2006 HLA-C locus alleles may modulate the clinical expression of psoriatic arthritis. Arthritis research & therapy 50 17166285
2020 Population Difference in Allele Frequency of HLA-C*05 and Its Correlation with COVID-19 Mortality. Viruses 49 33233780
2016 HLA-C Level Is Regulated by a Polymorphic Oct1 Binding Site in the HLA-C Promoter Region. American journal of human genetics 49 27817866
2021 Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C. Nature communications 48 33846289
2017 Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese. The Journal of investigative dermatology 48 29031612
2017 NLRP2 is a suppressor of NF-ƙB signaling and HLA-C expression in human trophoblasts†,‡. Biology of reproduction 45 28340094
2004 Mapping of the major psoriasis-susceptibility locus (PSORS1) in a 70-Kb interval around the corneodesmosin gene (CDSN). American journal of human genetics 43 15529278
1997 Molecular basis of HLA-C recognition by p58 natural killer cell inhibitory receptors. Journal of immunology (Baltimore, Md. : 1950) 42 9378975
2017 Melanocytes: Target Cells of an HLA-C*06:02-Restricted Autoimmune Response in Psoriasis. The Journal of investigative dermatology 40 28941475
1986 An HLA-C-specific DNA probe. Immunogenetics 38 3456979
2017 HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells. Cell host & microbe 37 28704647
2006 HLA-C mismatch is associated with inferior survival after unrelated donor non-myeloablative hematopoietic stem cell transplantation. Bone marrow transplantation 37 16532020
2006 HLA-C and KIR genes in hepatitis C virus infection. Human immunology 37 16571411
2013 Killer cell immunoglobulin-like receptor (KIR) genes and their HLA-C ligands in a Ugandan population. Immunogenetics 35 23974321
1997 HLA-C genes and susceptibility to type 1 autoimmune hepatitis. Hepatology (Baltimore, Md.) 35 9328330
2014 HLA-C*12:02 is a susceptibility factor in late-onset type of psoriasis in Japanese. The Journal of dermatology 34 25099155
2020 The Roles of Uterine Natural Killer (NK) Cells and KIR/HLA-C Combination in the Development of Preeclampsia: A Systematic Review. BioMed research international 32 32309433
2012 HLA-C and HIV-1: friends or foes? Retrovirology 32 22571741
2008 The PSORS1 locus gene CCHCR1 affects keratinocyte proliferation in transgenic mice. Human molecular genetics 32 18174193
1997 HLA-C revisited. Ten years of change. Immunologic research 32 9212365
2004 Transgenic mouse models support HCR as an effector gene in the PSORS1 locus. Human molecular genetics 30 15190014
2021 The New Kid on the Block: HLA-C, a Key Regulator of Natural Killer Cells in Viral Immunity. Cells 29 34831331
2010 Distribution of killer cell immunoglobulin-like receptors (KIR) and their HLA-C ligands in two Iranian populations. Immunogenetics 28 19936734
1988 Cloning and analysis of HLA class I cDNA encoding a new HLA-C specificity Cx52. Immunogenetics 28 2843461
2014 High-allelic variability in HLA-C mRNA expression: association with HLA-extended haplotypes. Genes and immunity 27 24500399
2019 HLA-C: An Accomplice in Rheumatic Diseases. ACR open rheumatology 26 31777841
2018 Identification of an elaborate NK-specific system regulating HLA-C expression. PLoS genetics 26 29329284
2000 HLA-C expression on platelets: studies with an HLA-Cw1-specific human monoclonal antibody. Vox sanguinis 26 11054049
1999 HLA-G and HLA-C at the feto-maternal interface: lessons learned from pathogenic viruses. Seminars in cancer biology 26 10092549
2018 HLA-C downregulation by HIV-1 adapts to host HLA genotype. PLoS pathogens 25 30180214
2012 Quantity of HLA-C surface expression and licensing of KIR2DL+ natural killer cells. Immunogenetics 25 22772778
2002 Molecular diversity of the HLA-C gene identified in a caucasian population. Human immunology 25 12072195
2020 Tuning of human NK cells by endogenous HLA-C expression. Immunogenetics 24 32219494
2010 HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion. Journal of reproductive immunology 24 21134695
2018 HLA-C*06:02-independent, gender-related association of PSORS1C3 and PSORS1C1/CDSN single-nucleotide polymorphisms with risk and severity of psoriasis. Molecular genetics and genomics : MGG 23 29589160
2017 ERAP1 and HLA-C interaction in inflammatory bowel disease in the Spanish population. Innate immunity 23 28651467
2014 Indirectly Recognized HLA-C Mismatches and Their Potential Role in Transplant Outcome. Frontiers in immunology 23 24860572
2011 KIR and HLA-C interactions promote differential dendritic cell maturation and is a major determinant of graft failure following kidney transplantation. PloS one 23 21912600
2014 HLA-C Incompatibilities in Allogeneic Unrelated Hematopoietic Stem Cell Transplantation. Frontiers in immunology 22 24904572
2013 HSV-2 specifically down regulates HLA-C expression to render HSV-2-infected DCs susceptible to NK cell killing. PLoS pathogens 22 23555244
2015 HLA-C and TNF gene polymorphisms are associated with psoriasis in Brazilian patients. International journal of dermatology 21 26470763
2013 Association analysis of the HLA-C gene in Japanese alopecia areata. Immunogenetics 21 23588886
2011 Tumor necrosis factor promoter polymorphism TNF*-857 is a risk allele for psoriatic arthritis independent of the PSORS1 locus. Arthritis and rheumatism 21 22127698
2010 HLA-C polymorphisms and PCR dropout in exons 2 and 3 of the Cw*0706 allele in sequence-based typing for unrelated Chinese marrow donors. Human immunology 21 20226825
2010 Counteraction of HLA-C-mediated immune control of HIV-1 by Nef. Journal of virology 21 20463068
2009 HLA-C matching and liver transplants: donor-recipient genotypes influence early outcome and CD8+KIR2D+ T-cells recuperation. Transplantation 21 19667963
2021 ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure. Frontiers in immunology 20 34745129
2023 "HLA-C: evolution, epigenetics, and pathological implications in the major histocompatibility complex". Frontiers in genetics 19 37465164
2016 HLA-C*01 is a Risk Factor for Crohn's Disease. Inflammatory bowel diseases 19 26891255
2016 Hypermethylation of HLA-C may be an epigenetic marker in psoriasis. Journal of dermatological science 19 27132688
2010 Comparison of MHC class I risk haplotypes in Thai and Caucasian psoriatics shows locus heterogeneity at PSORS1. Tissue antigens 19 20604894
2006 HLA-C expression pattern is spatially different between psoriasis and eczema skin lesions. The Journal of investigative dermatology 19 17008885
1990 Functional expression of HLA-C blank antigens on human blood lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 19 2246509
2016 HLA-C levels impact natural killer cell subset distribution and function. Human immunology 18 27521484
2008 Association analysis of the skin barrier gene cystatin A at the PSORS5 locus in psoriatic patients: evidence for interaction between PSORS1 and PSORS5. European journal of human genetics : EJHG 18 18364739
2004 Role of a KIR/HLA-C allorecognition system in pregnancy. Journal of reproductive immunology 18 15288178
2011 A study of KIR genes and HLA-C in Vogt-Koyanagi-Harada disease in Saudi Arabia. Molecular vision 17 22219647
2022 Association between HLA-C alleles and COVID-19 severity in a pilot study with a Spanish Mediterranean Caucasian cohort. PloS one 16 35960731
2022 Molecular interactions of PCSK9 with an inhibitory nanobody, CAP1 and HLA-C: Functional regulation of LDLR levels. Molecular metabolism 16 36566984
1997 HLA-C and -Bw typing of couples with unexplained recurrent miscarriages. Journal of reproductive immunology 16 9501290
2017 HIV-1 Env associates with HLA-C free-chains at the cell membrane modulating viral infectivity. Scientific reports 15 28051183
2014 Implication of HLA-C and KIR alleles in human papillomavirus infection and associated cervical lesions. Viral immunology 15 25188020
2005 Fine mapping of the psoriasis susceptibility gene PSORS1: a reassessment of risk associated with a putative risk haplotype lacking HLA-Cw6. The Journal of investigative dermatology 15 15854032
2022 HLA-B*07:02 and HLA-C*07:02 are associated with trimethoprim-sulfamethoxazole respiratory failure. The pharmacogenomics journal 14 35169303
2022 Functional HLA-C expressing trophoblast spheroids as a model to study placental-maternal immune interactions during human implantation. Scientific reports 14 35715452
2020 Single Nucleotide Polymorphism in KIR2DL1 Is Associated With HLA-C Expression in Global Populations. Frontiers in immunology 14 32983108
2008 HLA-C increases HIV-1 infectivity and is associated with gp120. Retrovirology 14 18673537
2022 T cells discriminate between groups C1 and C2 HLA-C. eLife 13 35587797

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