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. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages).[1]
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. The presence of DRB5 is linked with allelic variants of DRB1, otherwise it is omitted. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9.[1]
Lau M, Terasaki PI, Park MS (1995). "International Cell Exchange, 1994". Clinical transplants: 467–88. PMID7547576.
Dong RP, Kimura A, Sasazuki T (1992). "Sequence analysis of three novel DRw14-DRB1 alleles". Immunogenetics. 36 (2): 130–3. doi:10.1007/BF00215291. PMID1612646.
Piatier-Tonneau D, Gastinel LN, Amblard F, et al. (1991). "Interaction of CD4 with HLA class II antigens and HIV gp120". Immunogenetics. 34 (2): 121–8. doi:10.1007/BF00211424. PMID1869305.
Nong Y, Kandil O, Tobin EH, et al. (1991). "The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1". Cell. Immunol. 132 (1): 10–6. doi:10.1016/0008-8749(91)90002-S. PMID1905983.
Rosenstein Y, Burakoff SJ, Herrmann SH (1990). "HIV-gp120 can block CD4-class II MHC-mediated adhesion". J. Immunol. 144 (2): 526–31. PMID1967269.
Callahan KM, Fort MM, Obah EA, et al. (1990). "Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor". J. Immunol. 144 (9): 3341–6. PMID1970352.
Petersdorf EW, Griffith RL, Erlich HA, et al. (1990). "Unique sequences for two HLA-DRB1 genes expressed on distinct DRw6 haplotypes". Immunogenetics. 32 (2): 96–103. doi:10.1007/BF00210446. PMID1975801.
Lee KW, Johnson AH, Hurley CK (1990). "Two divergent routes of evolution gave rise to the DRw13 haplotypes". J. Immunol. 145 (9): 3119–25. PMID2212675.
Gorski J (1989). "HLA-DR beta-chain polymorphism. Second domain polymorphism reflects evolutionary relatedness of alleles and may explain public serologic epitopes". J. Immunol. 143 (1): 329–33. PMID2471740.
Clayton LK, Sieh M, Pious DA, Reinherz EL (1989). "Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding". Nature. 339 (6225): 548–51. doi:10.1038/339548a0. PMID2543930.
Hurley CK, Gregersen PK, Gorski J, et al. (1989). "The DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci". Hum. Immunol. 25 (1): 37–50. doi:10.1016/0198-8859(89)90068-2. PMID2565895.
Diamond DC, Sleckman BP, Gregory T, et al. (1988). "Inhibition of CD4+ T cell function by the HIV envelope protein, gp120". J. Immunol. 141 (11): 3715–7. PMID2846691.
Freeman SM, Saunders TL, Madden M, et al. (1987). "Comparison of DR beta 1 alleles from diabetic and normal individuals". Hum. Immunol. 19 (1): 1–6. doi:10.1016/0198-8859(87)90033-4. PMID2884201.
Owerbach D, Rich C, Taneja K (1986). "Characterization of three HLA-DR beta genes isolated from an HLA-DR 3/4 insulin-dependent diabetic patient". Immunogenetics. 24 (1): 41–6. doi:10.1007/BF00372296. PMID3015788.
Wu S, Saunders TL, Bach FH (1987). "Polymorphism of human Ia antigens generated by reciprocal intergenic exchange between two DR beta loci". Nature. 324 (6098): 676–9. doi:10.1038/324676a0. PMID3099214.
Liu CP, Bach FH, Wu SK (1988). "Molecular studies of a rare DR2/LD-5a/DQw3 HLA class II haplotype. Multiple genetic mechanisms in the generation of polymorphic HLA class II genes". J. Immunol. 140 (10): 3631–9. PMID3129499.
Steimle V, Hinkkanen A, Schlesier M, Epplen JT (1988). "A novel HLA-DR beta I sequence from the DRw11 haplotype". Immunogenetics. 28 (3): 208–10. doi:10.1007/BF00375861. PMID3137159.
1aqd: HLA-DR1 (DRA, DRB1 0101) HUMAN CLASS II HISTOCOMPATIBILITY PROTEIN (EXTRACELLULAR DOMAIN) COMPLEXED WITH ENDOGENOUS PEPTIDE
PDB 1d5m EBI.jpg
1d5m: X-RAY CRYSTAL STRUCTURE OF HLA-DR4 COMPLEXED WITH PEPTIDE AND SEB
PDB 1dlh EBI.jpg
1dlh: CRYSTAL STRUCTURE OF THE HUMAN CLASS II MHC PROTEIN HLA-DR1 COMPLEXED WITH AN INFLUENZA VIRUS PEPTIDE
PDB 1fv1 EBI.jpg
1fv1: STRUCTURAL BASIS FOR THE BINDING OF AN IMMUNODOMINANT PEPTIDE FROM MYELIN BASIC PROTEIN IN DIFFERENT REGISTERS BY TWO HLA-DR2 ALLELES
PDB 1fyt EBI.jpg
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
PDB 1jwm EBI.jpg
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)
PDB 1t5x EBI.jpg
1t5x: HLA-DR1 in complex with a synthetic peptide (AAYSDQATPLLLSPR) and the superantigen SEC3-3B2
PDB 1zgl EBI.jpg
1zgl: Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a
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
PDB 2icw EBI.jpg
2icw: Crystal structure of a complete ternary complex between TCR, superantigen, and peptide-MHC class II molecule
PDB 2ipk EBI.jpg
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
