Affinage

HLA-B

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

Round 2 corrected
Length
362 aa
Mass
40.5 kDa
Annotated
2026-04-28
130 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-B is a highly polymorphic MHC class I heavy chain that assembles with β2-microglobulin and short peptides in the endoplasmic reticulum—via tapasin-dependent or tapasin-independent pathways depending on allotype—and presents these peptide ligands at the cell surface for surveillance by CD8+ T cells and NK cells through TCR and KIR receptors (PMID:1525820, PMID:24790147, PMID:29995954). Allele-specific pockets in the peptide-binding groove, defined by high-resolution crystal structures, dictate the peptide repertoire: an Arg anchor at P2 governs HLA-B*27 binding, a conserved Arg62 accommodates phosphopeptides at P4 across many alleles, and the overall peptidome diversity varies markedly among allotypes (PMID:1922337, PMID:27920218, PMID:28514659). N-glycosylation of HLA-B is required for efficient KIR3DL1 engagement, and KIR3DS1 recognition of HLA-B*57:01 is peptide-dependent, linking viral peptide presentation to NK cell activation (PMID:26680341, PMID:25740999). Certain alleles confer disease susceptibility—HLA-B*27:05 presents self- and microbial peptides to cross-reactive public TCRs in ankylosing spondylitis and acute anterior uveitis, while HLA-B*15:02 and HLA-B*57:01 directly bind drugs (carbamazepine, flucloxacillin) to activate drug-specific CD8+ T cells in hypersensitivity reactions (PMID:36477533, PMID:22322005, PMID:33633747).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1976 High

    Establishing that HLA-B allotypic specificities and the Bw4/Bw6 serological epitopes reside on the same polypeptide chain resolved the molecular identity of HLA-B gene products and enabled subsequent structural analysis.

    Evidence Sequential immunoprecipitation of radiolabeled papain-solubilized lymphoblastoid membrane proteins with allele-specific and Bw4/Bw6 alloantisera

    PMID:63373

    Open questions at the time
    • No structural information on the chain architecture
    • Bw4/Bw6 epitope location on the polypeptide unknown
  2. 1992 High

    Crystal structures of HLA-B*27 revealed the molecular basis of peptide binding: nonameric peptides lie extended in the groove with termini anchored in conserved pockets and an Arg at P2 inserted into a B-allele-specific pocket, establishing the paradigm for allele-specific peptide selection.

    Evidence X-ray crystallography of HLA-B*27 at 2.1 Å resolution with bound self-peptides

    PMID:1525820 PMID:1922337

    Open questions at the time
    • Structures limited to B*27; generalizability to other HLA-B alleles not yet tested
    • Dynamics and conformational flexibility not captured by static crystal structures
  3. 1997 High

    Demonstration that HLA-B can present peptides via a TAP-independent pathway in TAP-deficient patients, and that HLA-B allotypes differ in peptide motifs and CD8-binding efficiency due to α3 domain polymorphisms, expanded the functional scope of HLA-B beyond the classical TAP-dependent pathway.

    Evidence Peptide elution and CTL assays from TAP-deficient B-LCL; peptide pool sequencing and CD8-binding mutagenesis (Thr245Ala) in 221-cell transfectants

    PMID:9089095 PMID:9144467 PMID:9331948

    Open questions at the time
    • Molecular mechanism of TAP-independent peptide loading unknown
    • CD8-binding polymorphism tested for only one allotype
  4. 1998 Medium

    Mapping transcriptional regulation showed that c-Myc and p53 each independently repress the HLA-B core promoter through the CCAAT/TATA region, providing a mechanism for MHC-I downregulation in tumors with oncogene activation or p53 overexpression.

    Evidence HLA-B promoter-reporter deletion constructs transfected into melanoma cells with varying c-Myc/p53 status

    PMID:8206526 PMID:9839551

    Open questions at the time
    • Direct transcription-factor–DNA binding not demonstrated
    • Relevance to endogenous HLA-B mRNA levels not confirmed in primary tumors
    • Chromatin context not assessed
  5. 1999 High

    HIV-1 Nef was shown to selectively downregulate HLA-A and HLA-B (but not HLA-C/E) by inducing endocytosis; the differential susceptibility maps to cytoplasmic tail differences, explaining how HIV evades CTL while sparing NK-inhibitory ligands.

    Evidence Flow cytometry, immunofluorescence, and subcellular fractionation in Nef-expressing cells; domain-swap and tail mutagenesis; NK and CTL cytotoxicity assays

    PMID:10403641 PMID:8612235

    Open questions at the time
    • Precise Nef–HLA-B tail interaction interface not structurally resolved
    • Relative contribution of endosomal degradation versus lysosomal routing unclear
  6. 2004 High

    A 1.5 Å structure of HLA-B*35:01 bound to a 14-mer peptide showed that long peptides are accommodated by central bulging while termini remain anchored, and that peptide conformation modulates TCR engagement, broadening understanding of peptide-length flexibility.

    Evidence X-ray crystallography of HLA-B*3501 with 14-mer and Ala-substituted peptide variants; CTL activation assays

    PMID:15494511

    Open questions at the time
    • Generalizability of bulging mechanism to other HLA-B alleles not tested
    • Structural basis of TCR contact with bulged peptides not resolved
  7. 2012 High

    Direct binding of carbamazepine to the HLA-B*15:02/peptide complex without antigen processing, and identification of key groove residues (Asn63, Ile95, Leu156) including conserved Arg62, established a structural mechanism for drug hypersensitivity mediated by drug–peptide–MHC interaction.

    Evidence SPR binding, peptide-binding assays, site-directed mutagenesis of HLA-B*1502, and CTL activation assays

    PMID:22322005

    Open questions at the time
    • No crystal structure of CBZ bound in the groove
    • In vivo relevance in patient tissue not confirmed
  8. 2014 High

    Systematic comparison across HLA-B allotypes revealed that polymorphic residues near the C-terminal groove determine tapasin dependence, and that tapasin-independent alleles refold more readily and resist viral TAP-inhibitor-mediated downregulation, explaining allotype-specific variation in antigen presentation efficiency.

    Evidence Surface expression in tapasin-deficient cells; in vitro refolding and aggregation assays across 27 HLA-B alleles; viral TAP-inhibitor experiments

    PMID:24790147 PMID:29995954

    Open questions at the time
    • Structural basis for tapasin interaction specificity not determined at atomic level
    • Clinical impact of tapasin independence on immune control not quantified
  9. 2016 High

    Discovery that the conserved Arg62 in HLA-B accommodates phosphopeptides at P4, combined with biophysical evidence that conformational dynamics differ between disease-associated (B*27:05) and non-disease-associated (B*27:09) subtypes, linked both peptide chemistry and heavy-chain dynamics to disease susceptibility.

    Evidence Immunopeptidomics and crystal structures of HLA-B*40/phosphopeptide; isotope-edited IR spectroscopy comparing B*27 subtypes; crystal structures of pVIPR–B*27:04 and B*27:06

    PMID:26748477 PMID:27920218

    Open questions at the time
    • Functional consequence of increased dynamics for TCR recognition not directly tested
    • Role of phosphopeptide presentation in immune surveillance in vivo unknown
  10. 2016 High

    Refined analysis of HIV Nef selectivity showed HLA-B is downregulated less efficiently than HLA-A, mapping the difference to Nef codon 202 and the absence of C-terminal CKV residues in HLA-B's cytoplasmic tail, revealing an allele-specific immune evasion hierarchy.

    Evidence Flow cytometry with 46 patient-derived Nef clones; Nef-202 mutagenesis; coculture T cell recognition assays

    PMID:26787826

    Open questions at the time
    • Crystal structure of Nef bound to HLA-B tail not available
    • Impact of differential downregulation on in vivo viral control not prospectively tested
  11. 2017 High

    HLA-B*46:01, formed by gene conversion between HLA-B and HLA-C, presents a uniquely low-diversity peptidome and engages KIR2DL3 in a peptide-dependent manner, illustrating how gene conversion events reshape both peptide repertoire and NK receptor recognition.

    Evidence High-resolution MS immunopeptidomics; KIR2DL3 binding assays

    PMID:28514659

    Open questions at the time
    • Structural basis of KIR2DL3 engagement by B*46:01 not determined
    • In vivo NK cell functional consequence not characterized
  12. 2022 High

    Identification of public cross-reactive TCRs (BV9-CDR3β/AV21) in HLA-B*27:05+ ankylosing spondylitis and uveitis patients, recognizing both self and microbial peptides presented by B*27:05 but not B*27:09, provided structural evidence that molecular mimicry through a shared TCR-binding motif underlies B*27-associated autoimmunity.

    Evidence HLA-B*27:05 yeast-display peptide library; TCR–pMHC crystal structures; T cell cloning from affected joint and eye tissues

    PMID:36477533

    Open questions at the time
    • Triggering microbial infection initiating disease not identified in patients
    • Whether targeting these public TCRs is therapeutically feasible is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the atomic-resolution structure of the tapasin–HLA-B editing complex; how conformational dynamics of disease-associated subtypes translate into altered TCR triggering thresholds in vivo; and the structural basis of Nef–HLA-B cytoplasmic tail interaction.
  • No atomic structure of tapasin–HLA-B complex
  • In vivo dynamics–TCR signaling relationship unresolved
  • Nef–HLA-B tail co-structure lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 7 GO:0005198 structural molecule activity 3
Localization
GO:0005886 plasma membrane 7 GO:0005783 endoplasmic reticulum 3 GO:0005768 endosome 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 11 R-HSA-1643685 Disease 5 R-HSA-392499 Metabolism of proteins 3
Partners
B2MKIR2DL3KIR3DL1KIR3DS1TAP1TAP2TAPBP
Complex memberships
HLA-B/β2-microglobulin/peptide heterotrimerMHC class I peptide-loading complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1976 HLA-B specificities (e.g., HLA-B7, HLA-B12) and the Bw4/Bw6 diallelic system are distinct antigenic determinants located on the same polypeptide chain, demonstrated by sequential immunoprecipitation of papain-solubilized membrane proteins with alloantisera to HLA-B7, HLA-B12, w4 and w6. Sequential immunoprecipitation of 125I-labeled papain-solubilized lymphoblastoid cell membrane proteins with HLA-B and Bw4/Bw6 alloantisera European journal of immunology High 63373
1991 Crystal structure of HLA-B27 reveals that nonameric self-peptides are bound in an extended conformation within the antigen-binding cleft, with peptide termini anchored in pockets and side chains at defined positions (especially Arg at position 2) contacting allele-specific pockets. X-ray crystallography Nature High 1922337
1992 The 2.1 Å crystal structure of HLA-B27 shows that tight peptide binding results from extensive contacts at both ends of the peptide cleft between main-chain atoms and conserved MHC side chains, and that the Arg anchor at peptide position 2 inserts into an HLA-B27-specific pocket, suggesting a general mechanism for peptide binding. X-ray crystallography at 2.1 Å resolution Cell High 1525820
1994 Transcriptional suppression of HLA-B expression by c-Myc overexpression is mediated through the core promoter region (a 43 bp fragment containing CCAAT and TATA elements), independently of enhancer A or enhancer B regions, indicating c-Myc interferes with basal transcription initiation. Transfection of HLA-B reporter constructs with variable promoter deletions into melanoma cell lines with high/low c-myc expression; heterologous enhancer coupling assay Immunogenetics Medium 8206526
1996 HIV-1 Nef protein induces rapid endocytosis of MHC class I molecules (including HLA-B) from the cell surface of lymphoid, monocytic and epithelial cells; Nef does not affect MHC-I synthesis or transport through the ER/cis-Golgi but causes surface MHC-I to accumulate in endosomal vesicles and undergo degradation. Expression of HIV-1 Nef in multiple cell types; immunofluorescence, subcellular fractionation, flow cytometry to track MHC-I trafficking Nature medicine High 8612235
1997 In TAP-deficient patients, the majority of cell-surface class I molecules are HLA-B products; two peptides eluted from these HLA-B molecules are derived from cytosolic proteins presented via a TAP-independent pathway, and an EBV LMP2-specific cytotoxic CD8+ T cell clone recognizes LMP2 presented by HLA-B on TAP-deficient cells. Cytofluorometry, biochemical analysis, peptide elution and sequencing from TAP-deficient EBV-transformed B-LCL, CTL cloning and cytotoxicity assays Journal of immunology High 9144467
1997 HLA-B*1501 presents a defined set of peptides with a consistent binding signature identified by large-scale production using hollow-fiber bioreactors combined with mass spectrometry, establishing that individual HLA-B alleles have allele-specific peptide-binding repertoires. Hollow-fiber bioreactor scale production of HLA-B*1501 plus bound peptides; mass spectrometry peptide mapping Immunogenetics Medium 9089095
1997 HLA-B*4801 selects nonamer peptides with Gln or Lys at position 2 and Leu at the C-terminus (defined by pool sequence analysis), and binds CD8α homodimers weakly due to Thr245 in the α3 domain; a Thr245Ala mutation restores CD8 binding to normal levels, yet alloreactive T cells recognizing B*4801 are still inhibited by anti-CD8 antibodies. Endogenous peptide pool sequencing from HLA-class-I-deficient 221 cell transfectants; in vitro cell-cell CD8 binding assay; site-directed mutagenesis of Thr245Ala; flow cytometry Tissue antigens High 9331948
1998 Wild-type p53 represses the HLA-B core promoter, and c-Myc-induced HLA-B downregulation is independent of p53 because c-Myc suppresses the basal HLA-B promoter even in p53-null cell lines, demonstrating that c-Myc and p53 repress the minimal HLA-B promoter through independent mechanisms. Transfection of HLA-B core promoter reporter constructs in p53-null melanoma lines with and without c-myc; co-transfection of wild-type p53 Molecular immunology Medium 9839551
1999 HIV-1 Nef selectively downregulates HLA-A and HLA-B but not HLA-C or HLA-E from the cell surface; residues in the cytoplasmic tails of HLA-C and HLA-E protect them from Nef-mediated downregulation, allowing HIV-infected cells to escape NK cell lysis while evading CTL. Flow cytometry of HIV-1-infected lymphoid cells expressing defined HLA molecules; domain-swap and mutagenesis to identify protective HLA cytoplasmic tail residues; NK cell cytotoxicity assays Immunity High 10403641
2004 Crystal structure of HLA-B*3501 at 1.5 Å bound to an unusually long 14-mer peptide shows that the N- and C-termini are embedded in the A and F pockets (as for normal-length peptides) while the central region bulges flexibly out of the groove; two peptide variants with Ala substitutions at P2 or P2+P9 show altered flexibility and conformation and reduced T cell activation, implicating both peptide conformation and MHC α-helical dynamics in TCR engagement. X-ray crystallography at 1.5 Å; site-directed mutagenesis of peptide positions; T cell activation assays with CTL clones Journal of immunology High 15494511
2010 Large-scale direct biochemical analysis of HLA-B*2705-bound peptides (the 'peptidome') using recombinant soluble HLA-B27 secreted from chondrocytic and HeLa cells, combined with tandem MS, identified 1,268 B27 peptides and refined the B27 binding motif including a propensity for long peptides whose central residues bulge from the groove; candidate molecular mimicry peptides were found between human cartilage proteins and bacterial sequences. Recombinant soluble HLA-B*2705 immunoaffinity purification from cell lines; capillary LC-MS/MS; SILAC and iTRAQ quantitation Arthritis and rheumatism High 20112406
2012 Direct physical interaction between HLA-B*1502 protein (loaded with endogenous peptides) and carbamazepine (CBZ) activates CBZ-specific CTLs without intracellular drug metabolism or antigen processing; surface plasmon resonance and peptide-binding assays showed the HLA-B*1502/peptide/β2m complex binds CBZ and analogs sharing the 5-carboxamide tricyclic ring; site-directed mutagenesis identified three key residues in the peptide-binding groove (Asn63, Ile95, Leu156) with Asn63 being essential; computer modeling revealed preferred binding at the B pocket via Arg62 interaction. In vitro CTL expansion and activation; surface plasmon resonance; peptide-binding assay; site-directed mutagenesis; molecular dynamics modeling The Journal of allergy and clinical immunology High 22322005
2014 HLA-B polymorphisms profoundly influence the assembly characteristics of HLA-B molecules and the stability of their peptide-deficient forms; dependence on the assembly factor tapasin varies markedly among allotypes, with several polymorphic residues near the C-terminal end of the peptide groove being key determinants of tapasin-independent assembly; tapasin-independent allotypes refold more readily with peptides in vitro and show less aggregation during refolding. Flow cytometry of HLA-B surface expression in tapasin-deficient cells; in vitro refolding assays with defined peptides; aggregation assays; comparison across multiple HLA-B allotypes Journal of immunology High 24790147
2015 KIR3DS1 recognition of HLA-B*57:01 is peptide-dependent; structure-guided screening identified HIV-derived peptide epitopes presented by HLA-B*57:01 that facilitate productive KIR3DS1 binding, demonstrating that changes in the peptide repertoire during viral infection can trigger KIR3DS1 engagement and NK cell activation. Structure-driven peptide screening; binding assays between KIR3DS1 and HLA-B*57:01-peptide complexes; functional NK cell assays Journal of virology Medium 25740999
2016 Phosphorylation at peptide position 4 (P4) predominates in HLA-B-associated phosphopeptide ligands across multiple HLA-B alleles, dictated by the conserved Arg62 residue in the HLA-B heavy chain; crystal structures of HLA-B*40 bound to a phosphopeptide versus its non-phosphorylated counterpart confirmed structural accommodation of phospho-P4 by Arg62; preference for basic residues at P1 is allotype-dependent and linked to A-pocket structure. Immunopeptidomics (peptidomic workflow); peptide-binding assays; X-ray crystallography of HLA-B*40/phosphopeptide complex Molecular & cellular proteomics High 27920218
2016 Conformational flexibility is elevated in disease-associated HLA-B*27 subtypes (B*27:04 and B*27:05) compared to non-disease-associated subtypes (B*27:06 and B*27:09), as measured by isotope-edited IR spectroscopy; crystal structures of pVIPR-B*27:04 and pVIPR-B*27:06 show that B*27:04 presents the peptide in a single conventional conformation while B*27:06 shows dual conformation, separating dual peptide conformation from increased molecular dynamics as distinct structural features. X-ray crystallography; isotope-edited infrared (IR) spectroscopy to probe molecular dynamics Arthritis & rheumatology High 26748477
2016 HIV-1 Nef downregulates HLA-B less efficiently than HLA-A from the surface of HIV-infected cells; the differential effect maps to Nef codon 202 (confirmed by site-directed mutagenesis) and to C-terminal CKV residues present in HLA-A but absent in HLA-B cytoplasmic tails; the degree of HLA-B relative resistance correlates inversely with the ability of HIV-specific T cells to recognize infected cells. Flow cytometry of 46 patient-derived Nef clones; Nef site-directed mutagenesis; coculture T cell recognition assay; in silico Nef codon function analysis mBio High 26787826
2017 HLA-B*46:01, formed by intergenic mini-conversion between HLA-B*15:01 and HLA-C*01:02, carries the C1 epitope and is recognized by NK receptor KIR2DL3; high-resolution MS showed B*46:01 has a low-diversity peptidome distinct from its parental alleles; a minority (21%) of B*46:01 peptides sharing C-terminal characteristics serve as KIR2DL3 ligands, linking peptidome composition to NK receptor recognition. High-resolution mass spectrometry immunopeptidomics; KIR2DL3 binding assays; sequence analysis of mini-conversion Cell reports High 28514659
2018 Multiple HLA-B allotypes (~15% of 27 tested) are expressed at relatively high levels on the surface of TAP1- or TAP2-deficient cells and occur in partially peptide-receptive and EndoH-sensitive forms, indicating TAP-independent assembly; synergy between high peptide-loading efficiency, broad specificity for peptides from unconventional sources, and high intrinsic stability of the empty form underlies TAP-independent assembly of certain HLA-B*35, B*57 and B*15 alleles; TAP-independent allotypes are more resistant to viral TAP inhibitor-induced HLA-I downmodulation. Flow cytometry of 27 HLA-B alleles in TAP1/TAP2-deficient cells; EndoH sensitivity assay; peptide-binding/loading efficiency assays; viral TAP inhibitor experiments; NK cell activation assays PLoS pathogens High 29995954
2018 In HLA-B*27:05, empty or suboptimally loaded molecules can escape intracellular retention and reach the cell surface as β2m-free heavy chains; an artificial disulfide bond between residues 84 and 139 confers enhanced conformational stability to suboptimally loaded molecules; a general quality control mechanism in the early secretory pathway (conserved between mouse and human cells) distinguishes poorly loaded from optimally loaded MHC-I, but is allotype-specifically permissive for HLA-B*27:05. Cell-based transport/trafficking assays; disulfide bond engineering (Cys84-Cys139 mutagenesis); flow cytometry; comparison of murine and human cell lines PLoS one Medium 30071035
2019 Pro-inflammatory cytokines TNFα and IFNγ increase HLA-B allomorph expression in lung cancer cells, and elevated HLA-B expression independently drives significant changes in the HLA-bound immunopeptidome beyond those attributable to proteome changes alone. Quantitative immunopeptidomics; proteomics; cytokine stimulation; flow cytometry of HLA-B surface levels Frontiers in immunology Medium 30833945
2021 Flucloxacillin (FLX) directly modifies HLA-B*57:01 at Lys146 (covalent haptenation), alters anchor residue frequencies in the immunopeptidome (enriching peptides with C-terminal Trp and FLX-haptenated Lys), and haptenated peptides at P4 and P6 induce drug-specific CD8+ T cells in HLA-B*57:01-transgenic mice; FLX modification at K146 may also impair KIR-3DL or peptide interactions. Mass spectrometry-based immunopeptidomics; in vivo immunization of HLA-B*57:01-Tg mice with drug-haptenated peptides; CD8+ T cell assays Frontiers in immunology Medium 33633747
2022 CD8+ T cells bearing disease-associated public TCRs (BV9-CDR3β motif with AV21 pairing) clonally expanded in joint (AS) and eye (AAU) of HLA-B*27 patients recognize self-peptides and microbial peptides presented by HLA-B*27:05 but not B*27:09; structural analysis revealed that TCR cross-reactivity is rooted in a shared binding motif at the peptide-MHC interface engaged by the BV9-CDR3β TCRs; HLA-B*27:05 yeast display peptide libraries identified the activating peptides. HLA-B*27:05 yeast display peptide library screening; crystal structure of TCR–HLA-B*27:05–peptide complexes; T cell cloning from joint/eye; TCR sequencing Nature High 36477533
2015 N-glycosylation of HLA-B*57:01 is required for efficient KIR3DL1 binding; tunicamycin treatment (blocking the first step of N-glycosylation) significantly reduces KIR3DL1-Fc binding to HLA-B*57:01-expressing cells despite sustained HLA-B*57:01 surface expression, and decreases KIR3DL1ζ+ Jurkat reporter activation while increasing degranulation of primary KIR3DL1+ NK cell clones. Glycosylation enzyme inhibitor panel; KIR3DL1-Fc binding assay by flow cytometry; KIR3DL1ζ+ Jurkat reporter assay; primary NK cell degranulation assay PLoS one Medium 26680341

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 3645 19571811
1999 Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science (New York, N.Y.) 2377 10426993
1986 The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 1673 2420472
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 1362 16751776
2008 HLA-B*5701 screening for hypersensitivity to abacavir. The New England journal of medicine 1292 18256392
2004 Medical genetics: a marker for Stevens-Johnson syndrome. Nature 1267 15057820
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2007 A whole-genome association study of major determinants for host control of HIV-1. Science (New York, N.Y.) 1010 17641165
2002 Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet (London, England) 1007 11888582
2007 High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 1004 17785583
2010 The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science (New York, N.Y.) 985 21051598
2005 HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proceedings of the National Academy of Sciences of the United States of America 955 15743917
2002 Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nature genetics 928 12134147
1996 Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nature medicine 874 8612235
2009 HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature genetics 750 19483685
2012 Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nature genetics 737 22286218
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2011 Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nature genetics 729 21743469
2003 Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. The Journal of biological chemistry 708 12519789
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1999 The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 704 10403641
2012 A census of human soluble protein complexes. Cell 689 22939629
1991 The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 688 1922337
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2009 Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nature genetics 639 19525953
1992 The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell 615 1525820
2007 Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nature genetics 613 17496894
2002 Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science (New York, N.Y.) 610 12029127
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2011 Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. The New England journal of medicine 494 21428768
2004 Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proceedings of the National Academy of Sciences of the United States of America 336 15024131
1992 Unusual HLA-B alleles in two tribes of Brazilian Indians. Nature 258 1317015
2012 Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome. The Journal of allergy and clinical immunology 225 22322005
2013 Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clinical pharmacology and therapeutics 160 23695185
1995 Comprehensive, serologically equivalent DNA typing for HLA-B by PCR using sequence-specific primers (PCR-SSP). Tissue antigens 125 7792765
2022 Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides. Nature 122 36477533
2007 Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B. PLoS pathogens 121 17892322
2017 KIR3DL1/HLA-B Subtypes Govern Acute Myelogenous Leukemia Relapse After Hematopoietic Cell Transplantation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 118 28520526
1999 Association analysis between the MIC-A and HLA-B alleles in Japanese patients with Behçet's disease. Arthritis and rheumatism 84 10513813
2014 Distinct assembly profiles of HLA-B molecules. Journal of immunology (Baltimore, Md. : 1950) 78 24790147
1997 Episodic evolution and turnover of HLA-B in the indigenous human populations of the Americas. Tissue antigens 76 9331945
1976 HLA-B specificities and w4, w6 specificities are on the same polypeptide. European journal of immunology 75 63373
2015 Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1. Journal of virology 69 25740999
2004 Conformational restraints and flexibility of 14-meric peptides in complex with HLA-B*3501. Journal of immunology (Baltimore, Md. : 1950) 69 15494511
1997 Large-scale production of class I bound peptides: assigning a signature to HLA-B*1501. Immunogenetics 61 9089095
2010 The HLA-B*2705 peptidome. Arthritis and rheumatism 58 20112406
2002 Association of ankylosing spondylitis with HLA-B*1403 in a West African population. Arthritis and rheumatism 57 12428239
2018 A transgenic mouse model for HLA-B*57:01-linked abacavir drug tolerance and reactivity. The Journal of clinical investigation 55 29782330
2012 Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. Journal of virology 53 22238317
2006 Diversity of MICA and linkage disequilibrium with HLA-B in two North American populations. Human immunology 52 16698437
1994 The HLA-B73 antigen has a most unusual structure that defines a second lineage of HLA-B alleles. Tissue antigens 51 7524186
2016 A Molecular Basis for the Presentation of Phosphorylated Peptides by HLA-B Antigens. Molecular & cellular proteomics : MCP 48 27920218
2002 A weak association of HLA-B*2702 with Behçet's disease. Genes and immunity 47 12209364
1995 Rational design of nonnatural peptides as high-affinity ligands for the HLA-B*2705 human leukocyte antigen. Proceedings of the National Academy of Sciences of the United States of America 47 7846047
1998 Association of clinical manifestations with HLA-B alleles in Takayasu arteritis. International journal of cardiology 46 9951811
2019 Pro-inflammatory Cytokines Alter the Immunopeptidome Landscape by Modulation of HLA-B Expression. Frontiers in immunology 44 30833945
2004 Transmission of HIV-1 and HLA-B allele-sharing within serodiscordant heterosexual Zambian couples. Lancet (London, England) 44 15220037
2017 An Update on the Genetic Polymorphism of HLA-B*27 With 213 Alleles Encompassing 160 Subtypes (and Still Counting). Current rheumatology reports 41 28247302
2017 Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease. Current rheumatology reports 39 28386763
2017 The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands. Cell reports 39 28514659
2018 The role of HLA-B*27 in spondyloarthritis. Best practice & research. Clinical rheumatology 38 30509441
2010 Evolution of the HIV-1 nef gene in HLA-B*57 positive elite suppressors. Retrovirology 37 21059238
2018 Selected HLA-B allotypes are resistant to inhibition or deficiency of the transporter associated with antigen processing (TAP). PLoS pathogens 33 29995954
2014 KIR diversity in Māori and Polynesians: populations in which HLA-B is not a significant KIR ligand. Immunogenetics 33 25139336
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