HLA-DRB5 explained

HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 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. 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]

See also

• HLA-DR

Further reading

• Lau M, Terasaki PI, Park MS . International Cell Exchange, 1994. . Clinical Transplants . 467–88 . 1995 . 7547576 .
• 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, et al . 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 .
• Petersdorf EW, Griffith RL, Erlich HA, etal . Unique sequences for two HLA-DRB1 genes expressed on distinct DRw6 haplotypes. . Immunogenetics . 32 . 2 . 96–103 . 1990 . 1975801 . 10.1007/BF00210446 . 28007432 .
• 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 . 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 . 1989 . 10.4049/jimmunol.143.1.329 . 2471740 . free .
• 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 .
• Hurley CK, Gregersen PK, Gorski J, etal . The DR3(w18),DQw4 haplotype differs from DR3(w17),DQw2 haplotypes at multiple class II loci. . Hum. Immunol. . 25 . 1 . 37–50 . 1989 . 2565895 . 10.1016/0198-8859(89)90068-2 . free .
• Diamond DC, Sleckman BP, Gregory T, et al . 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 .
• Freeman SM, Saunders TL, Madden M, et al . Comparison of DR beta 1 alleles from diabetic and normal individuals. . Hum. Immunol. . 19 . 1 . 1–6 . 1987 . 2884201 . 10.1016/0198-8859(87)90033-4 .
• Lee BS, Rust NA, McMichael AJ, McDevitt HO . HLA-DR2 subtypes form an additional supertypic family of DR beta alleles. . Proc. Natl. Acad. Sci. U.S.A. . 84 . 13 . 4591–5 . 1987 . 2885840 . 10.1073/pnas.84.13.4591 . 305136 . 1987PNAS...84.4591L . 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 .
• 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 .
• Liu CP, Bach FH, Wu SK . 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 . 1988 . 10.4049/jimmunol.140.10.3631 . 3129499 . free .
• Steimle V, Hinkkanen A, Schlesier M, Epplen JT . A novel HLA-DR beta I sequence from the DRw11 haplotype. . Immunogenetics . 28 . 3 . 208–10 . 1988 . 3137159 . 10.1007/BF00375861 . 2712069 .

Notes and References

1. Web site: Entrez Gene: HLA-DRB5 major histocompatibility complex, class II, DR beta 5.