HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1gene.[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.
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]
Prevalence of the HLA-DRB1*10:01 allele was greatly increased in people with anti-IgLON5 disease.[3]
↑Gregersen PK, Silver J, Winchester RJ (November 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. PMID2446635.
↑Gaig C, Graus F, Compta Y, Högl B, Bataller L, Brüggemann N, Giordana C, Heidbreder A, Kotschet K, Lewerenz J, Macher S, Martí MJ, Montojo T, Pérez-Pérez J, Puertas I, Seitz C, Simabukuro M, Téllez N, Wandinger KP, Iranzo A, Ercilla G, Sabater L, Santamaría J, Dalmau J (May 2017). "Clinical manifestations of the anti-IgLON5 disease". Neurology. 88 (18): 1736–1743. doi:10.1212/WNL.0000000000003887. PMC5409845. PMID28381508.
Further reading
Turesson C, Matteson EL (January 2006). "Genetics of rheumatoid arthritis". Mayo Clinic Proceedings. 81 (1): 94–101. doi:10.4065/81.1.94. PMID16438485.
Ahmad T, Marshall SE, Jewell D (June 2006). "Genetics of inflammatory bowel disease: the role of the HLA complex". World Journal of Gastroenterology. 12 (23): 3628–35. doi:10.3748/wjg.v12.i23.3628. PMID16773677.
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. PMID17329717.
1aqd: HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE
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1bx2: CRYSTAL STRUCTURE OF HLA-DR2 (DRA*0101,DRB1*1501) COMPLEXED WITH A PEPTIDE FROM HUMAN MYELIN BASIC PROTEIN
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1d5m: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB
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1d5x: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH DIPEPTIDE MIMETIC AND SEB
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1d5z: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDOMIMETIC AND SEB
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1d6e: CRYSTAL STRUCTURE OF HLA-DR4 COMPLEX WITH PEPTIDOMIMETIC AND SEB
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1dlh: CRYSTAL STRUCTURE OF THE HUMAN CLASS II MHC PROTEIN HLA-DR1 COMPLEXED WITH AN INFLUENZA VIRUS PEPTIDE
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1fv1: STRUCTURAL BASIS FOR THE BINDING OF AN IMMUNODOMINANT PEPTIDE FROM MYELIN BASIC PROTEIN IN DIFFERENT REGISTERS BY TWO HLA-DR2 ALLELES
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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
PDB 1h15 EBI.jpg
1h15: X-RAY CRYSTAL STRUCTURE OF HLA-DRA1*0101/DRB5*0101 COMPLEXED WITH A PEPTIDE FROM EPSTEIN BARR VIRUS DNA POLYMERASE
PDB 1hqr EBI.jpg
1hqr: CRYSTAL STRUCTURE OF A SUPERANTIGEN BOUND TO THE HIGH-AFFINITY, ZINC-DEPENDENT SITE ON MHC CLASS II
PDB 1hxy EBI.jpg
1hxy: CRYSTAL STRUCTURE OF STAPHYLOCOCCAL ENTEROTOXIN H IN COMPLEX WITH HUMAN MHC CLASS II
PDB 1j8h EBI.jpg
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
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1jwm: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1(HA peptide 306-318) with the Superantigen SEC3
PDB 1jws EBI.jpg
1jws: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the Superantigen SEC3 Variant 3B1
PDB 1jwu EBI.jpg
1jwu: Crystal Structure of the Complex of the MHC Class II Molecule HLA-DR1 (HA peptide 306-318) with the superantigen SEC3 Variant 3B2
PDB 1kg0 EBI.jpg
1kg0: Structure of the Epstein-Barr Virus gp42 Protein Bound to the MHC class II Receptor HLA-DR1
PDB 1klg EBI.jpg
1klg: Crystal structure of HLA-DR1/TPI(23-37, Thr28-->Ile mutant) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
PDB 1klu EBI.jpg
1klu: Crystal structure of HLA-DR1/TPI(23-37) complexed with staphylococcal enterotoxin C3 variant 3B2 (SEC3-3B2)
PDB 1lo5 EBI.jpg
1lo5: Crystal structure of the D227A variant of Staphylococcal enterotoxin A in complex with human MHC class II
PDB 1pyw EBI.jpg
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)
PDB 1r5i EBI.jpg
1r5i: Crystal structure of the MAM-MHC complex
PDB 1seb EBI.jpg
1seb: COMPLEX OF THE HUMAN MHC CLASS II GLYCOPROTEIN HLA-DR1 AND THE BACTERIAL SUPERANTIGEN SEB
PDB 1sje EBI.jpg
1sje: HLA-DR1 complexed with a 16 residue HIV capsid peptide bound in a hairpin conformation
PDB 1sjh EBI.jpg
1sjh: HLA-DR1 complexed with a 13 residue HIV capsid peptide
PDB 1t5w EBI.jpg
1t5w: HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR)
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1t5x: HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2
PDB 1ymm EBI.jpg
1ymm: TCR/HLA-DR2b/MBP-peptide complex
PDB 1zgl EBI.jpg
1zgl: Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a
PDB 2fse EBI.jpg
2fse: Crystallographic structure of a rheumatoid arthritis MHC susceptibility allele, HLA-DR1 (DRB1*0101), complexed with the immunodominant determinant of human type II collagen
PDB 2g9h EBI.jpg
2g9h: Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC class II Molecule
PDB 2iam EBI.jpg
2iam: Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
PDB 2ian EBI.jpg
2ian: Structural basis for recognition of mutant self by a tumor-specific, MHC class II-restricted TCR
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2icw: Crystal structure of a complete ternary complex between TCR, superantigen, and peptide-MHC class II molecule
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2ipk: Crystal Structure of the MHC Class II Molecule HLA-DR1 in Complex with the Fluorogenic Peptide, AcPKXVKQNTLKLAT (X=3-[5-(dimethylamino)-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl]-L-alanine) and the Superantigen, SEC3 Variant 3B2
PDB 2oje EBI.jpg
2oje: Mycoplasma arthritidis-derived mitogen complexed with class II MHC molecule HLA-DR1/HA complex in the presence of EDTA
PDB 2seb EBI.jpg
2seb: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH A PEPTIDE FROM HUMAN COLLAGEN II
