HLA-DRB4 explained

Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.^[1]

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. 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. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9.^[1]

See also

• HLA-DR

Further reading

• Germain RN . Binding domain regulation of MHC class II molecule assembly, trafficking, fate, and function. . Semin. Immunol. . 7 . 6 . 361–72 . 1996 . 8775462 . 10.1006/smim.1995.0041 .
• O'Brien RM, Cram DS, Russ GR, etal . Nucleotide sequences of the HLA-DRw12 and DRw8 B1 chains from an Australian aborigine. . Hum. Immunol. . 34 . 2 . 147–51 . 1992 . 1358866 . 10.1016/0198-8859(92)90041-K .
• Kenter M, Otting N, Anholts J, etal . Mhc-DRB diversity of the chimpanzee (Pan troglodytes). . Immunogenetics . 37 . 1 . 1–11 . 1992 . 1428007 . 10.1007/BF00223539 . 26557301 .
• Dong RP, Kimura A, Sasazuki T . Sequence analysis of three novel DRw14-DRB1 alleles. . Immunogenetics . 36 . 2 . 130–3 . 1992 . 1612646 . 10.1007/BF00215291 . 32928324 .
• Piatier-Tonneau D, Gastinel LN, Amblard F, etal . Interaction of CD4 with HLA class II antigens and HIV gp120. . Immunogenetics . 34 . 2 . 121–8 . 1991 . 1869305 . 10.1007/BF00211424 . 10116507 .
• Nong Y, Kandil O, Tobin EH, etal . 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 . 1991 . 1905983 . 10.1016/0008-8749(91)90002-S .
• Rosenstein Y, Burakoff SJ, Herrmann SH . HIV-gp120 can block CD4-class II MHC-mediated adhesion. . J. Immunol. . 144 . 2 . 526–31 . 1990 . 10.4049/jimmunol.144.2.526 . 1967269 . free .
• Callahan KM, Fort MM, Obah EA, etal . Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor. . J. Immunol. . 144 . 9 . 3341–6 . 1990 . 10.4049/jimmunol.144.9.3341 . 1970352 . free .
• Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ . Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. . Proc. Natl. Acad. Sci. U.S.A. . 87 . 22 . 9052–6 . 1991 . 1978941 . 10.1073/pnas.87.22.9052 . 55099 . free .
• Gyllensten UB, Sundvall M, Erlich HA . Allelic diversity is generated by intraexon sequence exchange at the DRB1 locus of primates. . Proc. Natl. Acad. Sci. U.S.A. . 88 . 9 . 3686–90 . 1991 . 2023919 . 10.1073/pnas.88.9.3686 . 51517 . 1991PNAS...88.3686G . free .
• Lee KW, Johnson AH, Hurley CK . Two divergent routes of evolution gave rise to the DRw13 haplotypes. . J. Immunol. . 145 . 9 . 3119–25 . 1990 . 10.4049/jimmunol.145.9.3119 . 2212675 . 19868100 .
• Gorski J . First domain sequence of the HLA-DRB1 chain from two HLA-DRw14 homozygous typing cell lines: TEM (Dw9) and AMALA (Dw16). . Hum. Immunol. . 24 . 2 . 145–9 . 1989 . 2466818 . 10.1016/0198-8859(89)90054-2 .
• Fan WM, Kasahara M, Gutknecht J, etal . Shared class II MHC polymorphisms between humans and chimpanzees. . Hum. Immunol. . 26 . 2 . 107–21 . 1990 . 2511168 . 10.1016/0198-8859(89)90096-7 .
• Clayton LK, Sieh M, Pious DA, Reinherz EL . Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. . Nature . 339 . 6225 . 548–51 . 1989 . 2543930 . 10.1038/339548a0 . 1989Natur.339..548C . 4246781 . free .
• Abe A, Ito I, Ohkubo M, etal . Two distinct subtypes of the HLA-DRw12 haplotypes in the Japanese population detected by nucleotide sequence analysis and oligonucleotide genotyping. . Immunogenetics . 30 . 6 . 422–6 . 1990 . 2592019 . 10.1007/BF02421173 . 30397455 .
• Diamond DC, Sleckman BP, Gregory T, etal . Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. . J. Immunol. . 141 . 11 . 3715–7 . 1988 . 10.4049/jimmunol.141.11.3715 . 2846691 . free .
• Owerbach D, Rich C, Taneja K . Characterization of three HLA-DR beta genes isolated from an HLA-DR 3/4 insulin-dependent diabetic patient. . Immunogenetics . 24 . 1 . 41–6 . 1986 . 3015788 . 10.1007/BF00372296 . 19599710 .
• Karr RW, Gregersen PK, Obata F, etal . Analysis of DR beta and DQ beta chain cDNA clones from a DR7 haplotype. . J. Immunol. . 137 . 9 . 2886–90 . 1986 . 10.4049/jimmunol.137.9.2886 . 3020127 . free .
• Andersson G, Larhammar D, Widmark E, etal . Class II genes of the human major histocompatibility complex. Organization and evolutionary relationship of the DR beta genes. . J. Biol. Chem. . 262 . 18 . 8748–58 . 1987 . 10.1016/S0021-9258(18)47480-7 . 3036826 . free .
• Wu S, Saunders TL, Bach FH . Polymorphism of human Ia antigens generated by reciprocal intergenic exchange between two DR beta loci. . Nature . 324 . 6098 . 676–9 . 1987 . 3099214 . 10.1038/324676a0 . 4365990 .

Notes and References

1. Web site: Entrez Gene: HLA-DRB4 major histocompatibility complex, class II, DR beta 4.