HLA-DRB1

Major histocompatibility complex, class II, DR beta 1

Structure of HLA-DRB1 (green) complexed with HLA-DRA (cyan) and a fragment of HLA-A (magenta) based on the PDB: 1AQD coordinates

Available structures

PDB

Ortholog search: PDBe, RCSB

List of PDB id codes
1A6A, 1AQD, 1BX2, 1DLH, 1FYT, 1HXY, 1JWM, 1JWS, 1JWU, 1KG0, 1KLG, 1KLU, 1LO5, 1PYW, 1R5I, 1SEB, 1SJE, 1SJH, 1T5W, 1T5X, 1YMM, 2FSE, 2G9H, 2IAM, 2IAN, 2ICW, 2IPK, 2OJE, 2WBJ, 2XN9, 3L6F, 3PDO, 3PGC, 3PGD, 3QXA, 3QXD, 3S4S, 3S5L, 4AEN, 4AH2, 4C56, 4E41, 4FQX, 4GBX, 4I5B, 4OV5

Identifiers

Symbols

HLA-DRB1 ; DRB1; DRw10; HLA-DR1B; HLA-DRB; SS1

External IDs

OMIM: 142857 MGI: 95901 HomoloGene: 136635 GeneCards: HLA-DRB1 Gene

Gene ontology
Molecular function	• MHC class II protein complex binding • MHC class II receptor activity • peptide antigen binding
Cellular component	• Golgi membrane • lysosomal membrane • plasma membrane • integral component of plasma membrane • external side of plasma membrane • cell surface • ER to Golgi transport vesicle membrane • membrane • transport vesicle membrane • endocytic vesicle membrane • clathrin-coated endocytic vesicle membrane • late endosome membrane • trans-Golgi network membrane • MHC class II protein complex • extracellular exosome • integral component of lumenal side of endoplasmic reticulum membrane
Biological process	• immunoglobulin production involved in immunoglobulin mediated immune response • inflammatory response to antigenic stimulus • humoral immune response mediated by circulating immunoglobulin • peptide antigen assembly with MHC class II protein complex • polysaccharide assembly with MHC class II protein complex • immune response • viral process • detection of bacterium • cytokine-mediated signaling pathway • antigen processing and presentation of exogenous peptide antigen via MHC class II • T cell costimulation • regulation of interleukin-4 production • negative regulation of interferon-gamma production • positive regulation of insulin secretion involved in cellular response to glucose stimulus • T-helper 1 type immune response • negative regulation of T cell proliferation • T cell receptor signaling pathway • protein tetramerization • interferon-gamma-mediated signaling pathway • regulation of interleukin-10 secretion
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 6:
32.55 – 32.59 Mb

Chr 17:
34.31 – 34.32 Mb

PubMed search

HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene.^[1] DRB1 encodes the most prevalent beta subunit of HLA-DR. Several alleles of DRB1 (shared epitope alleles)^[2] are associated with an increased incidence of rheumatoid arthritis.

Function

The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins to T helper cells. Class II molecules are constitutively expressed in professional antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages),^[1] and could be induced in non-professional APCs.

Gene structure and polymorphisms

The beta chain is approximately 26-28 kDa. It is encoded by 6 exons, exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and typing for these polymorphisms is routinely done for bone marrow and kidney transplantation.^[1]

Gene expression

DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5. DRB1 is present in all individuals. Allelic variants of DRB1 are linked with either none or one of the genes DRB3, DRB4 and DRB5. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9.^[1]

References

1 2 3 4 "Entrez Gene: HLA-DRB1 major histocompatibility complex, class II, DR beta 1".
↑ Gregersen PK, Silver J, Winchester RJ (Nov 1987). "The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis". Arthritis and Rheumatism 30 (11): 1205–13. doi:10.1002/art.1780301102. PMID 2446635.

Turesson C, Matteson EL (Jan 2006). "Genetics of rheumatoid arthritis". Mayo Clinic Proceedings 81 (1): 94–101. doi:10.4065/81.1.94. PMID 16438485.
Ahmad T, Marshall SE, Jewell D (Jun 2006). "Genetics of inflammatory bowel disease: the role of the HLA complex". World Journal of Gastroenterology 12 (23): 3628–35. PMID 16773677.
Schmidt H, Williamson D, Ashley-Koch A (May 2007). "HLA-DR15 haplotype and multiple sclerosis: a HuGE review". American Journal of Epidemiology 165 (10): 1097–109. doi:10.1093/aje/kwk118. PMID 17329717.

PDB gallery

1aqd: HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE

1bx2: CRYSTAL STRUCTURE OF HLA-DR2 (DRA*0101,DRB1*1501) COMPLEXED WITH A PEPTIDE FROM HUMAN MYELIN BASIC PROTEIN

1d5m: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB

1d5x: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH DIPEPTIDE MIMETIC AND SEB

1d5z: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDOMIMETIC AND SEB

1d6e: CRYSTAL STRUCTURE OF HLA-DR4 COMPLEX WITH PEPTIDOMIMETIC AND SEB

1dlh: CRYSTAL STRUCTURE OF THE HUMAN CLASS II MHC PROTEIN HLA-DR1 COMPLEXED WITH AN INFLUENZA VIRUS PEPTIDE

1fv1: STRUCTURAL BASIS FOR THE BINDING OF AN IMMUNODOMINANT PEPTIDE FROM MYELIN BASIC PROTEIN IN DIFFERENT REGISTERS BY TWO HLA-DR2 ALLELES

1fyt: CRYSTAL STRUCTURE OF A COMPLEX OF A HUMAN ALPHA/BETA-T CELL RECEPTOR, INFLUENZA HA ANTIGEN PEPTIDE, AND MHC CLASS II MOLECULE, HLA-DR1

1h15: X-RAY CRYSTAL STRUCTURE OF HLA-DRA1*0101/DRB5*0101 COMPLEXED WITH A PEPTIDE FROM EPSTEIN BARR VIRUS DNA POLYMERASE

1hqr: CRYSTAL STRUCTURE OF A SUPERANTIGEN BOUND TO THE HIGH-AFFINITY, ZINC-DEPENDENT SITE ON MHC CLASS II

1hxy: CRYSTAL STRUCTURE OF STAPHYLOCOCCAL ENTEROTOXIN H IN COMPLEX WITH HUMAN MHC CLASS II

1j8h: Crystal Structure of a Complex of a Human alpha/beta-T cell Receptor, Influenza HA Antigen Peptide, and MHC Class II Molecule, HLA-DR4

1jwm: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1(HA peptide 306-318) with the Superantigen SEC3

1jws: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the Superantigen SEC3 Variant 3B1

1jwu: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the superantigen SEC3 Variant 3B2

1kg0: Structure of the Epstein-Barr Virus gp42 Protein Bound to the MHC class II Receptor HLA-DR1

1klg: Crystal structure of HLA-DR1/TPI(23-37, Thr28-->Ile mutant) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)

1klu: Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)

1lo5: Crystal structure of the D227A variant of Staphylococcal enterotoxin A in complex with human MHC class II

1pyw: Human class II MHC protein HLA-DR1 bound to a designed peptide related to influenza virus hemagglutinin, FVKQNA(MAA)AL, in complex with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)

1r5i: Crystal structure of the MAM-MHC complex

1seb: COMPLEX OF THE HUMAN MHC CLASS II GLYCOPROTEIN HLA-DR1 AND THE BACTERIAL SUPERANTIGEN SEB

1sje: HLA-DR1 complexed with a 16 residue HIV capsid peptide bound in a hairpin conformation

1sjh: HLA-DR1 complexed with a 13 residue HIV capsid peptide

1t5w: HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR)

1t5x: HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2

1ymm: TCR/HLA-DR2b/MBP-peptide complex

1zgl: Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a

2fse: Crystallographic structure of a rheumatoid arthritis MHC susceptibility allele, HLA-DR1 (DRB1*0101), complexed with the immunodominant determinant of human type II collagen

2g9h: Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule

2iam: Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

2ian: Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR

2icw: Crystal structure of a complete ternary complex between TCR, superantigen, and peptide-MHC class II molecule

Image:PDB_2oje_EBI.jpg

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Surface antigens

Major histocompatibility complex/
Human leukocyte antigen

MHC class I	HLA-A HLA-B HLA-C HLA-E HLA-F HLA-G

MHC class II	HLA-DM α β HLA-DO α β HLA-DP α1 β1 HLA-DQ α1 α2 β1 β2 β3 HLA-DR α β1 β3 β4 β5 Minor histocompatibility antigen

Other

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HLA-DRB1

Function

Gene structure and polymorphisms

Gene expression

See also

References

Further reading