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Gene Review

HLA-DRB3  -  major histocompatibility complex, class II...

Homo sapiens

Synonyms: HLA class II histocompatibility antigen, DR beta 3 chain, MHC class II antigen DRB3
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Disease relevance of HLA-DRB3

  • Furthermore, sharing of HLA-DRB3 and histologic evidence of rejection were associated with more rapid progression to bridging fibrosis both by univariate methods (chi2=4.12, P=0.04 and chi2=4.66, P=0.03 respectively), and by multivariate analysis (chi2=13.01, P=0.001) [1].
  • However, HLA-DRB3 * 0202 was seen in all children with multiple sclerosis [2].
  • These results suggest that the HLA-alleles responsible for the susceptibility to sarcoidosis are located at the HLA-DRB1 locus rather than the HLA-DRB3, -DQA1 and -DQB1 loci [3].
  • Eight (35%) of 23 partner pairs in which HIV-1 transmission did not occur were immunologically discordant at HLA-DRB3, compared with 0 of 11 partner pairs in which HIV-1 transmission did occur (P=.027) [4].
  • Rapid and simple subtyping of the HLA-DRB3 gene in Graves' disease by using temperature-gradient gel electrophoresis [5].

High impact information on HLA-DRB3

  • The DRw52a specificity was determined directly by hybridising HLA-DRB3 genes, group specifically amplified by the polymerase chain reaction, with an allele specific oligonucleotide probe, whereas in the previously mentioned study DRw52a was assigned by indirect serological criteria, which overestimate the frequency of this allele [6].
  • Here we show that for the human HLA-DRB1 and HLA-DRB3 gene products this ratio is controlled by the valine/glycine dimorphism at position 86 [7].
  • RESULTS: No statistically significant differences were observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes between the patients and a healthy control group [8].
  • The Indian and European haplotypes share HLA-B*0801, HLA-DRB1*0301 and HLA-DQB1*02 but differ for subtypes of HLA-Cw*07 and HLA-DRB3 and all central MHC alleles tested [9].
  • These alleles differ from other HLA-DRB3 alleles by previously undescribed single nucleotide polymorphisms [10].

Biological context of HLA-DRB3


Anatomical context of HLA-DRB3

  • HLA-restriction analysis showed that in addition to HLA-DRB1 products (serologically defined HLA-DR1 to HLA-DR10), the HLA molecules encoded by HLA-DRB3 (HLA-DR52) and HLA-DRB4 (HLA-DR53) are important in presentation of mycobacterial antigens and epitopes to T cells [15].
  • The polymorphic second exon of the HLA-DRB3 gene was amplified from four homozygous typing cell lines, 223 healthy individuals, and 102 patients with Graves' disease by using the PCR [5].

Associations of HLA-DRB3 with chemical compounds

  • This allele is of particular interest because it is very similar to HLA-DRB1*08 alleles (YSTGECY and lack of an associated HLA-DRB3 gene), but it lacks leucine at position 74, which is characteristic of all previously reported DRB1*08 alleles [16].
  • The relationship between HLA-DRB3 antigens and specific IgE responsiveness to highly purified major allergen from white birch (Betula verrucosa), Bet v I, was studied in 43 patients, who were skin-prick test positive to birch pollen extract [12].

Regulatory relationships of HLA-DRB3

  • The highly polymorphic HLA-DRB1 locus is always expressed at a higher level than the HLA-DRB3 locus, and functional assays indicate that the proximal promoter of DRB1 is indeed more active than that of DRB3 [17].

Other interactions of HLA-DRB3

  • Equivalents of the HLA-DRB1*02, -DRB1*03, -DRB1*07 allelic lineages and the HLA-DRB3, -DRB4, -DRB5, -DRB6, and -DRB7 loci were all found in the chimpanzee [18].
  • In DRB1-matched pairs the proliferation induced by HLA-DRB3, -DQ and -DP mismatches may be unmasked [19].
  • Korean BAC library construction and characterization of HLA-DRA, HLA-DRB3 [13].
  • This highly significant negative association with the HLA DRB3 allele DRw52a in whites persisted even when DR4- or DRw11(5)-positive individuals were excluded from the patient and control groups [20].

Analytical, diagnostic and therapeutic context of HLA-DRB3

  • Our data, based on DNA typing methods of HLA-D genes, provide evidence that the susceptibility is strongly associated with HLA-DRB3 genes [21].


  1. Donor-recipient sharing of HLA class II alleles predicts earlier recurrence and accelerated progression of hepatitis C following liver transplantation. Cotler, S.J., Gaur, L.K., Gretch, D.R., Wile, M., Strong, D.M., Bronner, M.P., Carithers, R.L., Emond, M.J., Perkins, J.D., Nelson, K.A. Tissue Antigens (1998) [Pubmed]
  2. Molecular analysis of HLA class II-associated susceptibility to neuroinflammatory diseases in Korean children. Oh, H.H., Kwon, S.H., Kim, C.W., Choe, B.H., Ko, C.W., Jung, H.D., Suh, J.S., Lee, J.H. J. Korean Med. Sci. (2004) [Pubmed]
  3. Molecular genetic studies of HLA class II alleles in sarcoidosis. Ishihara, M., Ohno, S., Ishida, T., Ando, H., Naruse, T., Nose, Y., Inoko, H. Tissue Antigens (1994) [Pubmed]
  4. Discordance at human leukocyte antigen-DRB3 and protection from human immunodeficiency virus type 1 transmission. Hader, S.L., Hodge, T.W., Buchacz, K.A., Bray, R.A., Padian, N.S., Rausa, A., Slaviniski, S.A., Holmberg, S.D. J. Infect. Dis. (2002) [Pubmed]
  5. Rapid and simple subtyping of the HLA-DRB3 gene in Graves' disease by using temperature-gradient gel electrophoresis. Chen, M., Maerz, W., Manfras, B.J., Kuehnl, P., Usadel, K.H., Boehm, B.O. Hum. Immunol. (1993) [Pubmed]
  6. HLA class II genes in primary sclerosing cholangitis and chronic inflammatory bowel disease: no HLA-DRw52a association in Swedish patients with sclerosing cholangitis. Zetterquist, H., Broomé, U., Einarsson, K., Olerup, O. Gut (1992) [Pubmed]
  7. HLA-DR beta chain residue 86 controls DR alpha beta dimer stability. Verreck, F.A., Termijtelen, A., Koning, F. Eur. J. Immunol. (1993) [Pubmed]
  8. HLA-DRB genotypes in Japanese patients with renal cell carcinoma. Kojima, Y., Takahara, S., Nonomura, N., Sada, M., Tsuji, T., Hatori, M., Fujioka, H., Kuroda, H., Miki, T., Okuyama, A. Oncology (2000) [Pubmed]
  9. Common HLA-B8-DR3 haplotype in Northern India is different from that found in Europe. Witt, C.S., Price, P., Kaur, G., Cheong, K., Kanga, U., Sayer, D., Christiansen, F., Mehra, N.K. Tissue Antigens (2002) [Pubmed]
  10. Novel HLA-DRB3 alleles discovered during routine sequencing based typing, DRB3*02023, DRB3*0212, DRB3*0213 and DRB3*03012. Greville, W.D., Kennedy, A., Chapman, G., Dunckley, H. Tissue Antigens (2002) [Pubmed]
  11. HLA-DRB3 typing by restriction digestion of locus-specific amplified DNA. Smrzka, O.W., Faé, I., Pickl, W.F., Fischer, G.F. Tissue Antigens (1991) [Pubmed]
  12. Association between HLA-DRB3*0101 and immunoglobulin-E responsiveness to Bet v I. Sparholt, S.H., Georgsen, J., Madsen, H.O., Svendsen, U.G., Schou, C. Hum. Immunol. (1994) [Pubmed]
  13. Korean BAC library construction and characterization of HLA-DRA, HLA-DRB3. Park, M.H., Lee, H.J., Bok, J., Kim, C.H., Hong, S.T., Park, C., Kimm, K., Oh, B., Lee, J.Y. J. Biochem. Mol. Biol. (2006) [Pubmed]
  14. Pregnancy-associated autoimmune neonatal thrombocytopenia: role of maternal HLA genotype. Gandemer, V., Kaplan, C., Quelvennec, E., Poulain, P., Laurent, M.C., Semana, G., Renouard, J., Le Gall, E. Br. J. Haematol. (1999) [Pubmed]
  15. HLA-restricted immune response to mycobacterial antigens: relevance to vaccine design. Mustafa, A.S. Hum. Immunol. (2000) [Pubmed]
  16. Molecular analysis of HLA-DRB1*08/12 alleles: identification of two additional alleles. Eberle, M., Baxter-Lowe, L.A. Hum. Immunol. (1992) [Pubmed]
  17. The different level of expression of HLA-DRB1 and -DRB3 genes is controlled by conserved isotypic differences in promoter sequence. Emery, P., Mach, B., Reith, W. Hum. Immunol. (1993) [Pubmed]
  18. Mhc-DRB diversity of the chimpanzee (Pan troglodytes). Kenter, M., Otting, N., Anholts, J., Jonker, M., Schipper, R., Bontrop, R.E. Immunogenetics (1992) [Pubmed]
  19. HLA-DP incompatibilities induce significant proliferation in primary mixed lymphocyte cultures in HLA-A, -B, -DR and -DQ compatible individuals: implications for allogeneic bone marrow transplantation. Olerup, O., Möller, E., Persson, U. Tissue Antigens (1990) [Pubmed]
  20. HLA-D locus associations in alopecia areata. DRw52a may confer disease resistance. Duvic, M., Hordinsky, M.K., Fiedler, V.C., O'Brien, W.R., Young, R., Reveille, J.D. Archives of dermatology. (1991) [Pubmed]
  21. HLA-DRB3 gene alleles in Caucasian patients with Graves' disease. Boehm, B.O., Kühnl, P., Manfras, B.J., Chen, M., Lee, J.C., Holzberger, G., Seidl, S., Schifferdecker, E., Schumm-Draeger, P.M., Usadel, K.H. The Clinical investigator. (1992) [Pubmed]
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