HLA-DRB5

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

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).

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.

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.

See also

• HLA-DR

Further reading

• Lau M, Terasaki PI, Park MS (1995). "International Cell Exchange, 1994". Clinical transplants: 467–88. PMID 7547576.
• Dong RP, Kimura A, Sasazuki T (1992). "Sequence analysis of three novel DRw14-DRB1 alleles". Immunogenetics. 36 (2): 130–3. doi:10.1007/BF00215291. PMID 1612646.
• 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. PMID 1869305.
• 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. PMID 1905983.
• Rosenstein Y, Burakoff SJ, Herrmann SH (1990). "HIV-gp120 can block CD4-class II MHC-mediated adhesion". J. Immunol. 144 (2): 526–31. PMID 1967269.
• 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. PMID 1970352.
• 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. PMID 1975801.
• Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ (1991). "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. doi:10.1073/pnas.87.22.9052. PMC 55099. PMID 1978941.
• Gyllensten UB, Sundvall M, Erlich HA (1991). "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. doi:10.1073/pnas.88.9.3686. PMC 51517. PMID 2023919.
• Lee KW, Johnson AH, Hurley CK (1990). "Two divergent routes of evolution gave rise to the DRw13 haplotypes". J. Immunol. 145 (9): 3119–25. PMID 2212675.
• 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. PMID 2471740.
• 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. PMID 2543930.
• 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. PMID 2565895.
• 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. PMID 2846691.
• 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. PMID 2884201.
• Lee BS, Rust NA, McMichael AJ, McDevitt HO (1987). "HLA-DR2 subtypes form an additional supertypic family of DR beta alleles". Proc. Natl. Acad. Sci. U.S.A. 84 (13): 4591–5. doi:10.1073/pnas.84.13.4591. PMC 305136. PMID 2885840.
• 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. PMID 3015788.
• 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. PMID 3099214.
• 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. PMID 3129499.
• 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. PMID 3137159.