Affinage

HLA-DRB1

HLA class II histocompatibility antigen, DRB1 beta chain · UniProt P01911

Round 2 corrected
Length
266 aa
Mass
30.0 kDa
Annotated
2026-04-28
130 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-DRB1 encodes the polymorphic β1 chain of the MHC class II HLA-DR αβ heterodimer, which binds antigenic peptides in an extended conformation within an open-ended groove stabilized by 12 conserved hydrogen bonds to the peptide backbone and allele-specific anchor pockets—particularly a hydrophobic P1 pocket and a charge-variable P4 pocket whose residues (β71, β74, β86) dictate selective binding of peptides including citrullinated self-antigens (PMID:8145819, PMID:24190431, PMID:22286218). HLA-DM catalyzes dissociation of the invariant chain–derived CLIP peptide at acidic pH, enabling antigenic peptide loading in endosomal compartments, with exchange kinetics governed by the completeness of C-terminal anchor pocket occupation (PMID:7606781, PMID:32010139). Allele-specific peptide presentation shapes the peripheral CD4+ T-cell receptor repertoire through thymic selection and determines susceptibility to autoimmune diseases including rheumatoid arthritis, type 1 diabetes, and anti-GBM glomerulonephritis (PMID:8770633, PMID:23411782, PMID:34153873). Beyond antigen presentation, the disease-associated shared epitope motif encoded within the third hypervariable region functions as an extracellular signal transduction ligand that activates osteoclastogenesis and pro-inflammatory macrophage polarization, while protective allele-encoded epitopes drive anti-inflammatory polarization (PMID:23180817, PMID:33510427).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1993 High

    Determination of the first HLA-DR1 crystal structure resolved how the class II groove accommodates peptide and revealed αβ heterodimer dimerization, establishing the structural framework for understanding DRB1 polymorphism and peptide binding.

    Evidence X-ray crystallography of HLA-DR1

    PMID:8316295

    Open questions at the time
    • No peptide-bound structure yet available at this stage
    • Functional significance of αβ dimer-of-dimers not experimentally tested
  2. 1994 High

    Co-crystal structures and systematic binding assays defined the universal peptide-binding mode—12 backbone hydrogen bonds plus a dominant hydrophobic P1 anchor—explaining how a single groove accommodates diverse peptides while conserving the binding register.

    Evidence X-ray crystallography of HLA-DR1–HA peptide complex; quantitative competitive binding assays with alanine-scan, reduced-bond, and N-methyl analogues on DRB1*0101 and *0401

    PMID:8144889 PMID:8145819

    Open questions at the time
    • Contributions of P4 and other secondary pockets to allele-specific binding not yet structurally resolved
    • Role of non-classical anchor positions in autoantigen binding unknown
  3. 1995 High

    HLA-DM was shown to catalyze CLIP dissociation from DR at acidic pH, revealing the enzymatic editing step required for peptide loading in endosomal compartments and explaining how the invariant chain intermediate is resolved.

    Evidence In vitro biochemical dissociation assay with antibody blocking and pH titration

    PMID:7606781

    Open questions at the time
    • Structural basis of HLA-DM–DR interaction not determined
    • Kinetic differences in DM-mediated exchange across DRB1 alleles not yet characterized
  4. 1995 Medium

    DRB1 allelic polymorphism was shown to shape the peripheral CD4+ TCR Vβ repertoire through thymic selection, establishing that DRB1 variation influences immune competence upstream of any specific antigen encounter.

    Evidence TCR Vβ repertoire analysis by flow cytometry/PCR in HLA-typed donor cohorts comparing naive versus memory CD4+ T cells

    PMID:8770633

    Open questions at the time
    • Mechanism of allele-specific positive/negative selection not dissected at the peptide level
    • Limited to correlative cohort data without experimental perturbation
  5. 1996 Medium

    Peptide elution from RA-associated (DRB1*0404) versus non-RA-associated (DRB1*0402) allomorphs revealed distinct self-peptide repertoires, demonstrating that allele-specific groove chemistry selects different endogenous ligands with potential relevance to autoimmunity.

    Evidence Immunoaffinity purification, HPLC fractionation, Edman degradation, and tandem mass spectrometry from B cell lines

    PMID:8892091

    Open questions at the time
    • Link between specific self-peptide repertoires and disease pathogenesis not functionally tested
    • Single-laboratory study with limited cell line diversity
  6. 2012 High

    Fine-mapping of MHC association with RA resolved disease risk to three amino acid positions in the DRβ1 peptide-binding groove (positions 11, 71, 74), pinpointing the structural basis of genetic susceptibility beyond traditional allele-level associations.

    Evidence Genome-wide SNP imputation of HLA alleles and amino acid polymorphisms in ~20,000 individuals with conditional analysis

    PMID:22286218

    Open questions at the time
    • Causal peptide(s) mediating RA risk through these positions not identified
    • Independent contributions of positions 11, 71, 74 to specific pocket properties not structurally verified
  7. 2012 High

    The shared epitope motif was shown to function as an antigen-presentation-independent signal transduction ligand activating osteoclastogenesis and Th17 differentiation, establishing a non-canonical immunomodulatory role for the DRB1-encoded surface.

    Evidence In vitro osteoclastogenesis assays (mouse and human), SE-transgenic mice, collagen-induced arthritis model with histology and cytokine measurement

    PMID:23180817

    Open questions at the time
    • Receptor for the SE ligand on target cells not identified
    • Signaling pathway downstream of SE engagement not fully elucidated
  8. 2013 High

    Crystal structures of DRB1*04:01 versus *04:02 with citrullinated peptides explained how P4 pocket charge (electropositive in *04:01, electronegative in *04:02) selectively accommodates citrulline, providing the structural mechanism by which RA-risk alleles present citrullinated self-antigens to CD4+ T cells.

    Evidence X-ray crystallography, peptide elution/mass spectrometry, HLA-II tetramer staining and T cell functional assays in DRB1*04:01+ donors

    PMID:24190431

    Open questions at the time
    • Range of citrullinated epitopes naturally presented in vivo not fully catalogued
    • Whether citrulline-specific T cells are sufficient for RA initiation remains untested
  9. 2013 High

    Allele-specific pathogenic potential was demonstrated when DRB1*15:01-restricted CD4+ T cell clones recognizing a collagen IV epitope transferred crescentic glomerulonephritis upon adoptive transfer, directly linking DRB1 allele-restricted antigen presentation to organ-specific autoimmune disease.

    Evidence Adoptive transfer of T cell clones into HLA-DRB1*15:01 versus *01:01 transgenic mice with renal histology and functional assessment

    PMID:23411782

    Open questions at the time
    • Whether additional DRB1 alleles confer risk for anti-GBM disease through alternative epitopes is unknown
    • Contribution of DRB1*15:01-restricted T cells relative to B cell/antibody-mediated injury not delineated
  10. 2020 Medium

    HLA-DM-catalyzed peptide exchange kinetics were shown to depend on complete occupation of C-terminal anchor pockets (P6/7, P9), explaining why certain autoantigen peptides (e.g., MBP) are inefficiently loaded despite adequate groove affinity and refining the understanding of DM editing as a selectivity filter.

    Evidence Recombinant HLA-DRB1*01:01 protein, DM-catalyzed CLIP exchange kinetics, chimeric MBP–HA peptide analysis

    PMID:32010139

    Open questions at the time
    • Generalizability across DRB1 alleles not tested
    • In vivo relevance of slow exchange kinetics for autoimmune epitope presentation not established
  11. 2021 Medium

    Antigen-presentation-incompetent peptides from protective versus risk-associated DRB1 alleles were shown to differentially polarize macrophages toward anti-inflammatory (M2) or pro-inflammatory (M1) transcriptomes, extending the non-canonical signaling role of DRB1 allelic sequences beyond osteoclastogenesis to innate immune regulation.

    Evidence RNA-sequencing of in vitro macrophages treated with AP-incompetent synthetic DRB1 allelic peptides, upstream regulator analysis

    PMID:33510427

    Open questions at the time
    • Cell-surface receptor mediating allelic peptide recognition on macrophages not identified
    • In vivo contribution of macrophage polarization to disease protection/susceptibility not demonstrated
    • Single laboratory, no independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor and downstream signaling pathway through which shared epitope and protective DRB1-derived peptides modulate innate immune cell polarization and osteoclastogenesis remain unidentified, representing the central open question bridging DRB1 non-canonical signaling to disease mechanism.
  • No receptor identified for SE peptide signaling
  • No structural basis for how free DRB1 peptides engage target cells
  • In vivo physiological relevance of non-canonical signaling pathway not confirmed in human disease

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005768 endosome 2 GO:0005886 plasma membrane 2 GO:0005576 extracellular region 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-1643685 Disease 5
Partners
CD4HLA-DMAHLA-DMBHLA-DRA
Complex memberships
MHC class II αβ heterodimer (HLA-DRA/HLA-DRB1)

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 X-ray crystal structure of HLA-DR1 (an HLA-DRB1-containing heterodimer) revealed that peptides bind in an extended conformation in an open-ended groove, with a prominent non-polar pocket near one end accommodating an anchoring peptide side chain; a dimer of the class II αβ heterodimers was observed, suggesting dimerization as a mechanism for cytoplasmic signalling. X-ray crystallography Nature High 8316295
1994 Crystal structure of HLA-DR1 complexed with an influenza hemagglutinin peptide (HA306-318) showed the peptide binds in an extended, twisted conformation; five of thirteen side chains are accommodated in pockets in the binding site; twelve hydrogen bonds between conserved HLA-DR1 residues and peptide main-chain amide bonds provide a universal mode of peptide binding distinct from MHC class I. X-ray crystallography Nature High 8145819
1994 Peptide binding to HLA-DRB1*0101 and DRB1*0401 requires a hydrophobic amino acid near the peptide amino-terminus that docks into a conserved pocket; aromatic side chains are superior to aliphatic at this position; the majority of binding free energy arises from hydrogen bonds between conserved binding-site residues and peptide backbone amide bonds, not side-chain contacts; optimal binding depends on position of the hydrophobic anchor relative to peptide termini. Quantitative competitive peptide binding assay with systematic alanine-scan analogues, reduced peptide bonds, and N-methyl amino acid substitutions Journal of Immunology High 8144889
1995 HLA-DM catalyzes the dissociation of the invariant chain-derived CLIP peptide from MHC class II (HLA-DR) αβ dimers in vitro, facilitating loading of antigenic peptides; the reaction has an acidic pH optimum consistent with occurrence in lysosomal compartments; antibody blocking experiments indicate a transient HLA-DM–MHC class II interaction is required. In vitro biochemical dissociation assay, antibody blocking, pH titration Cell High 7606781
1995 A quantitative database of the contribution of each of the 20 amino acids at 11 positions of a simplified peptide backbone was used to predict peptide binding affinity to HLA-DRB1*0401; the model accurately predicted binding of 13 unrelated peptides and identified two high-affinity myelin basic protein epitopes corresponding to DRB1*0401-restricted T cell determinants, validating that a key hydrophobic residue at position 3 relative to the peptide register drives binding. Quantitative peptide binding assay, combinatorial peptide library, T cell hybridoma specificity testing Journal of Immunology High 7751636
1995 Comparison of TCR Vβ segment usage in cohorts of individuals expressing distinct HLA-DRB1 alleles showed a correlation between DRB1 allele and Vβ usage in naive (CD45RO−) CD4+ T cells, demonstrating that HLA-DRB1 allelic polymorphism shapes the peripheral CD4+ T cell TCR repertoire through thymic selection; antigenic experience (CD45RO+ memory cells) modulates but does not eliminate this DRB1-imposed Vβ profile. TCR Vβ repertoire analysis by flow cytometry/PCR in HLA-typed donor cohorts, comparison of naive vs memory CD4+ T cell subsets Human Immunology Medium 8770633
1996 Naturally processed peptides eluted from HLA-DRB1*0404 (RA-associated) and DRB1*0402 (non-RA-associated) B cell lines were predominantly nested clusters derived from HLA class I (B and C) α-chain sequences; DRB1*0404 loaded peptides from positions 26–43 of HLA-B/C α-chain, while DRB1*0402 loaded peptides from positions 129–145, demonstrating allele-specific differences in which self-peptides naturally occupy the groove. Immunoaffinity purification of MHC class II complexes, reversed-phase HPLC fractionation, Edman degradation sequencing, tandem mass spectrometry Journal of Neuroscience Research Medium 8892091
1998 Introduction of the HLA-DRB1*1502 (DR2) transgene into collagen-induced arthritis-susceptible HLA-DQ8 mice significantly decreased disease incidence and induced a Th2 cytokine profile, whereas DRB1*0301 (DR3) had no protective effect and maintained a Th1 profile; DR molecules were confirmed functional by positive/negative selection of the Vβ T cell repertoire, demonstrating that DRB1 polymorphism can modulate DQ-restricted autoimmune arthritis. Transgenic mouse model (double DR/DQ transgenic in class II-deficient background), collagen-induced arthritis, in vitro T cell proliferation, cytokine analysis, TCR Vβ repertoire analysis International Immunology Medium 9796911
2003 HLA class II (including HLA-DRB1-encoded DR) molecules are abundantly present in B cell-derived exosomes and are concentrated in cholesterol/sphingomyelin/GM3-enriched detergent-resistant membrane domains (lipid rafts) within multivesicular bodies, whereas plasma membrane-associated MHC class II is readily solubilized; this compartmentalization may facilitate protein sorting into internal vesicles of multivesicular bodies. Proteomic analysis of purified exosomes by mass spectrometry, detergent solubility fractionation (CHAPS), electron microscopy, immunofluorescence Journal of Biological Chemistry Medium 12519789
2012 The HLA-DRB1 shared epitope (SE) sequence motif acts as a signal transduction ligand that activates osteoclastogenesis independently of antigen presentation: SE peptides potently stimulated osteoclast differentiation in mouse and human cells in vitro, enhanced production of pro-osteoclastogenic factors, and promoted Th17 cell differentiation expressing RANKL; IL-17 and SE synergistically enhanced osteoclast differentiation; SE transgenic mice showed higher osteoclastogenesis ex vivo; in vivo administration to collagen-induced arthritis mice increased arthritis severity, synovial osteoclast abundance, and bone erosion. In vitro osteoclastogenesis assay (mouse and human cells), transgenic mouse model (HLA-DRB1 SE-expressing), collagen-induced arthritis model, cytokine measurement, histology Journal of Immunology High 23180817
2013 Citrullinated aggrecan and vimentin epitopes bind to HLA-DRB1*04:01/04 because citrulline is accommodated within the electropositive P4 pocket of these allomorphs; in contrast, the electronegative P4 pocket of RA-resistant HLA-DRB1*04:02 interacts with arginine or citrulline indiscriminately. Peptide elution studies confirmed P4 arginine-containing peptides from DRB1*04:02 but not DRB1*04:01/04. Citrullination altered protease susceptibility of vimentin, generating epitopes presented to CD4+ T cells specifically in HLA-DRB1*04:01+ individuals. Crystal structure determination, peptide elution/mass spectrometry, HLA-II tetramer staining of peripheral blood CD4+ T cells, T cell functional assays The Journal of Experimental Medicine High 24190431
2013 The HLA-DRB1*15:01-restricted T cell epitope α3136-146 from the α3 chain of type IV collagen (Goodpasture antigen) was identified and shown to be naturally processed; CD4+ T cell clones specific for this epitope transferred necrotizing crescentic glomerulonephritis, albuminuria, and renal impairment into naïve HLA-DRB1*15:01 transgenic mice but not HLA-DRB1*01:01 transgenic mice, demonstrating allele-specific pathogenic T cell priming. HLA-DRB1*15:01 and *01:01 transgenic mouse immunization, T cell clone generation, adoptive transfer disease model, histology, renal function assessment Journal of the American Society of Nephrology High 23411782
2013 Dendritic cells present FVIII-derived peptides on HLA-DR (including HLA-DRB1) with optimal presentation 12–24 hours after maturation, persisting for 96 hours; immature DCs retain half of FVIII-loaded MHC class II intracellularly, while mature DCs display the majority on the plasma membrane; macrophages internalize FVIII as efficiently as DCs but present fewer peptides with different epitopes; five HLA-promiscuous FVIII peptide regions were identified across 8 donors. HLA class II immunoprecipitation, mass spectrometric peptide identification, flow cytometry for MHC II surface/intracellular distribution, time-course antigen presentation studies PLoS ONE Medium 24244658
2012 Fine-mapping of MHC association with seropositive RA identified that three amino acid positions in HLA-DRβ1 (positions 11, 71, and 74), which are located in the peptide-binding groove, almost completely explain the MHC association to RA risk, along with single positions in HLA-B (position 9) and HLA-DPβ1 (position 9); conditional analyses demonstrated these positions are independent of each other. Genome-wide SNP imputation of HLA classical alleles and amino acid polymorphisms in 5,018 RA cases and 14,974 controls, conditional and haplotype analyses Nature Genetics High 22286218
2020 HLA-DRB1*01:01 binds newly identified myelin basic protein peptides (MBP153-161 and MBP90-98) with affinity comparable to influenza HA peptide, but HLA-DM-catalyzed CLIP exchange for MBP peptides is significantly slower than for HA peptide; chimeric peptide analysis showed this kinetic difference results from absence of anchor residues in the C-terminal part of MBP peptides, causing incomplete occupation of P6/7 and P9 pockets and failure of P1/P4 docking, leading to rapid peptide dissociation from HLA-DM–HLA-DR complex. Recombinant HLA-DRB1*01:01 protein production, peptide binding affinity measurements, HLA-DM-catalyzed CLIP exchange kinetics, chimeric MBP-HA peptide analysis Frontiers in Immunology Medium 32010139
2021 Short synthetic peptides corresponding to the third allelic hypervariable regions of disease risk-associated HLA-DRB1 alleles (SE-containing) versus protective alleles differentially polarize macrophages in vitro: risk allele peptides activate pro-inflammatory M1 transcriptomes while protective allele peptides activate anti-inflammatory M2 transcriptomes, as shown by RNA-sequencing; this immune modulation occurs independently of antigen presentation (AP-incompetent peptides used) and involves distinct upstream regulatory pathways. RNA-sequencing of in vitro-polarized macrophages, AP-incompetent synthetic HLA-DRB1 allelic peptides, gene ontology and upstream regulator analysis Scientific Reports Medium 33510427
2021 Three amino acid residues of HLA-DRB1 at positions β71, β74, and β86 determine T1D risk; the 'KAG' motif (corresponding to DRB1*04:01) is most strongly associated with disease and, through structural modeling, is shown to create specific differences in peptide antigen anchor pocket preferences at p1, p4, and p7, affecting differential binding of T1D autoantigens preproinsulin and GAD65. Population-based case-control HLA typing, birth cohort prospective islet autoantibody study, hierarchical sequence similarity analysis, HLA-peptide structural modeling EBioMedicine Medium 34153873
2009 A proteochemometrics model of peptide binding to 12 HLA-DRB1 proteins using z-descriptors for both peptide and protein sequences identified key peptide and protein positions involved in interactions, with hydrophobicity, steric bulk, and polarity at specific positions driving binding; models showed moderate goodness of fit (r²=0.685–0.732) and good cross-validated predictive ability. Computational proteochemometrics modeling of 2666 peptide-DRB1 binding data points, cross-validation, external test set prediction European Journal of Medicinal Chemistry Low 19896246

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The sequence of the human genome. Science (New York, N.Y.) 8428 11181995
2007 Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 7256 17554300
2012 Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 3725 23128233
2009 Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 3645 19571811
2013 Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature genetics 3440 24162737
1993 Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 2026 8316295
2013 Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 1778 24390342
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
1994 Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 1391 8145819
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
2011 Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nature genetics 1078 21297633
2010 Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nature genetics 1018 20453842
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
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
2010 PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations. Bioinformatics (Oxford, England) 908 20335276
2009 Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nature genetics 803 19838193
2012 Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nature genetics 737 22286218
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
2007 TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study. The New England journal of medicine 675 17804836
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
2008 HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 622 18252895
1995 HLA-DM induces CLIP dissociation from MHC class II alpha beta dimers and facilitates peptide loading. Cell 597 7606781
2004 Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation. Oncogene 547 15489916
2004 Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood 544 15191952
2009 Genomewide association study of leprosy. The New England journal of medicine 532 20018961
2011 Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nature genetics 522 21399633
1992 The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. Annals of internal medicine 452 1416553
2013 A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. The Journal of experimental medicine 331 24190431
2006 Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Human molecular genetics 250 16905561
1999 Polymorphisms in the SOD2 and HLA-DRB1 genes are associated with nonfamilial idiopathic dilated cardiomyopathy in Japanese. Biochemical and biophysical research communications 153 10425186
1992 Rapid HLA-DRB1 genotyping by nested PCR amplification. Tissue antigens 142 1574800
2007 HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis. PloS one 138 17653284
2010 The rheumatoid arthritis HLA-DRB1 shared epitope. Current opinion in rheumatology 133 20061955
1994 Exploration of requirements for peptide binding to HLA DRB1*0101 and DRB1*0401. Journal of immunology (Baltimore, Md. : 1950) 127 8144889
1998 Recent origin of HLA-DRB1 alleles and implications for human evolution. Nature genetics 110 9500545
1991 HLA-DRB1*01 subtyping by allele-specific PCR amplification: a sensitive, specific and rapid technique. Tissue antigens 102 1685264
1995 HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression. Digestive diseases and sciences 99 7720475
2004 Increased susceptibility to rheumatoid arthritis in Koreans heterozygous for HLA-DRB1*0405 and *0901. Arthritis and rheumatism 94 15529363
2006 Chronic periaortitis and HLA-DRB1*03: another clue to an autoimmune origin. Arthritis and rheumatism 91 16463424
2017 HLA-DRB1 the notorious gene in the mosaic of autoimmunity. Immunologic research 90 27435705
2012 Association between Parkinson's disease and the HLA-DRB1 locus. Movement disorders : official journal of the Movement Disorder Society 88 22807207
2020 Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis-From Research to Clinical Practice. Cells 87 32370106
2013 Association of HLA-DRB1-restricted CD4⁺ T cell responses with HIV immune control. Nature medicine 83 23793098
1998 Clinical significance of HLA-DRB1*0410 in Japanese patients with idiopathic thrombocytopenic purpura. Blood 75 9572996
2010 Multiple sclerosis, vitamin D, and HLA-DRB1*15. Neurology 67 20530326
2018 In Situ Humoral Immunity to Vimentin in HLA-DRB1*03+ Patients With Pulmonary Sarcoidosis. Frontiers in immunology 65 30038611
2008 Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population. Inflammatory bowel diseases 64 18338763
2013 The HLA-DRB1*15:01-restricted Goodpasture's T cell epitope induces GN. Journal of the American Society of Nephrology : JASN 63 23411782
2002 MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. The Journal of rheumatology 58 12022360
2000 HLA-DRB1, -DQA1, and -DQB1 genotypes in patients with nasal polyposis. The Laryngoscope 57 10718431
1995 Prediction of peptide affinity to HLA DRB1*0401. Journal of immunology (Baltimore, Md. : 1950) 56 7751636
2011 HLA-DRB1*15:01 and multiple sclerosis: a female association? Multiple sclerosis (Houndmills, Basingstoke, England) 55 22127897
2004 Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis. Arthritis and rheumatism 54 15529352
2000 Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele. Annals of the rheumatic diseases 53 10784518
1999 HLA-DRB1 genotype influences risk for and severity of rheumatoid arthritis. The Journal of rheumatology 50 10332964
2011 HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis. Arthritis and rheumatism 49 21280007
2003 Dissecting the associations of endemic pemphigus foliaceus (Fogo Selvagem) with HLA-DRB1 alleles and genotypes. Genes and immunity 49 12618858
2000 Independent contribution of HLA-DRB1 and TNF alpha promoter polymorphisms to the susceptibility to Crohn's disease. Genes and immunity 48 11196680
2015 Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans. American journal of respiratory cell and molecular biology 47 25506722
2009 Interaction of vitamin D receptor with HLA DRB1 0301 in type 1 diabetes patients from North India. PloS one 45 19956544
2016 The role of common protective alleles HLA-DRB1*13 among systemic autoimmune diseases. Genes and immunity 43 27829665
2017 IFNA-AS1 regulates CD4+ T cell activation in myasthenia gravis though HLA-DRB1. Clinical immunology (Orlando, Fla.) 40 28822831
2011 Genetic variants in the HLA-DRB1 gene are associated with Kashin-Beck disease in the Tibetan population. Arthritis and rheumatism 36 21739420
2020 Comprehensive meta-analysis reveals an association of the HLA-DRB1*1602 allele with autoimmune diseases mediated predominantly by autoantibodies. Autoimmunity reviews 35 32234402
2009 HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis. Tissue antigens 35 19392788
2015 The influence of HLA-DRB1*15 on motor cortical pathology in multiple sclerosis. Neuropathology and applied neurobiology 32 24964187
2013 Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever. Human immunology 31 23380141
2012 HLA-DRB1-DQB1 haplotypes confer susceptibility and resistance to multiple sclerosis in Sardinia. PloS one 31 22509268
2007 A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for autoantibody production in rheumatoid arthritis. Arthritis research & therapy 30 17328818
1998 Modulation of HLA-DQ-restricted collagen-induced arthritis by HLA-DRB1 polymorphism. International immunology 30 9796911
2012 Association of HLA-DRB1 alleles and neuropsychological function in autism. Psychiatric genetics 29 21716163
2013 Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII. PloS one 28 24244658
1994 Influence of HLA-DRB1 gene variation on the clinical course of Vogt-Koyanagi-Harada disease. Investigative ophthalmology & visual science 28 7906684
2011 Association between HLA-DRB1 and myasthenia gravis in a northern Han Chinese population. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 27 21924912
1995 High resolution HLA-DRB1 SSP typing for cadaveric donor transplantation. Tissue antigens 27 7725310
2012 Proinflammatory HLA-DRB1*01-haplotype predisposes to ST-elevation myocardial infarction. Atherosclerosis 26 22310063
2012 An HLA-DRB1-coded signal transduction ligand facilitates inflammatory arthritis: a new mechanism of autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 26 23180817
1996 HLA-DRB1, DQA1, DQB1 DNA polymorphism in the Bulgarian population. Tissue antigens 26 8851725
2006 Interaction of HLA-DRB1 alleles with CTLA-4 in the predisposition to Graves' disease: the impact of DRB1*07. Thyroid : official journal of the American Thyroid Association 25 16756466
2006 HLA DRB1*15-DPB1*05 haplotype: a susceptible gene marker for isocyanate-induced occupational asthma? Allergy 25 16792590
2003 Molecular analyses of HLA-DRB1, -DPB1, and -DQB1 in Jing ethnic minority of Southwest China. Human immunology 25 12878363
1999 Relative HLA-DRB1*13 allele frequencies and DRB3 associations of unrelated individuals from five US populations. Human immunology 25 10566602
1991 HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes in Japanese multiple sclerosis patients. Tissue antigens 25 1926126
2017 Genetic association of HLA-DRB1 multiple polymorphisms with dermatomyositis in Chinese population. HLA 24 29106035
2009 Anti-"Mi(a)" immunization is associated with HLA-DRB1*0901. Transfusion 24 19243543
2008 Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients. Clinical and experimental rheumatology 24 19210888
2014 A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population. Cancer medicine 23 24403192
2020 Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides. Frontiers in immunology 22 32010139
1997 The effect of HLA-DRB1 disease susceptibility markers on the expression of RA. Scandinavian journal of rheumatology 22 9433406
2017 Pooled analysis of the HLA-DRB1 by smoking interaction in Parkinson disease. Annals of neurology 21 28981958
2013 Association of HLA-DRB1*15:02 and DRB5*01:02 allele with the susceptibility to systemic sclerosis in Thai patients. Rheumatology international 21 23404077
2007 Analysis of HLA-DRB1, DQA1, DQB1 haplotypes in Sardinian centenarians. Experimental gerontology 21 17714903
2012 The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese. BMC medical genetics 19 22578019
2012 Association of HLA-DRB1*1501 tagging rs3135388 gene polymorphism with multiple sclerosis. Journal of neuroimmunology 19 23186557
2010 Human risk allele HLA-DRB1*0405 predisposes class II transgenic Ab0 NOD mice to autoimmune pancreatitis. Gastroenterology 19 20303356
1992 Generic HLA-DRB1 gene oligotyping by a nonradioactive reverse dot-blot methodology. Human immunology 19 1293086
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