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Gene Review

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

Homo sapiens

Synonyms: D6S221E, DMB, HLA class II histocompatibility antigen, DM beta chain, MHC class II antigen DMB, RING7, ...
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Disease relevance of HLA-DMB


High impact information on HLA-DMB

  • HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region, and shares some homology with MHC class I and class II proteins [5].
  • Expression of DMB complementary DNA in mutants lacking DMB messenger RNA restores the wild-type phenotype [6].
  • The metallointercalator Rh(phi)2DMB3+ (phi, 9,10-phenanthrenequinone diimine; DMB, 4,4'-dimethyl-2,2'-bipyridine) catalyzed the repair of a thymine dimer incorporated site-specifically in a 16-base pair DNA duplex by means of visible light [7].
  • In contrast, cells treated with C5-DMB-analogues of sphingomyelin or lactosylceramide internalized the fluorescent lipid into a punctate pattern of fluorescence during warming at 37 degrees C, and this process was temperature and energy dependent [8].
  • Together, alleles of single nucleotide polymorphisms at the DMB and DOB genes, and the microsatellite locus TNFc, identified approximately 40% of Sardinian DR3 haplotypes as non-predisposing [9].

Biological context of HLA-DMB


Anatomical context of HLA-DMB

  • The Val86/Val86 genotype was correlated with genotyping for other putative MS susceptibility genes, including T cell receptor beta chain germline polymorphisms, HLA-DMB alleles, and -DQA1 and -DQB1 alleles encoding critical amino acid residues, with a significant interaction only observed with DQB1 Leu26 (p = 0.014) [14].
  • The mRNA levels of LMP7, HLA-DMA, and HLA-DMB genes, all located within the HLA-D region, were analyzed in the "bare lymphocyte" line SJO, which had been shown to be characterized by a transcription defect of class II genes (DP, DQ, and DR) [15].
  • HLA-DMA and -DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells [16].
  • We conclude that the spacing of the HLA-DMB-encoded tyrosine motif relative to the transmembrane domain is an important feature controlling DM sorting in endosomes [17].
  • We examined the targeting signals and compartments involved in the intracellular trafficking of human HLA-DM by expressing hybrid molecules comprising the cytoplasmic domain of DMB and luminal and transmembrane domains of CD8 in HeLa cells [18].

Associations of HLA-DMB with chemical compounds

  • Both strain DMB and Methanospirillum hungatei utilized formate as a source of carbon and energy [19].
  • The class II region is better characterised, with evidence of one DRA, four DRB (one coding and three non-coding), one DQA1, two DQA2, and one each of the DQB1, DQB2, DNA, DOB, DYA, DYB, DMA, and DMB genes in the region [20].
  • The antihyperglycemic drug dimethylbiguanide (DMB, also known as metformin) reduces the risk of cardiovascular complications in type 2 diabetes, although the mechanism(s) involved are unclear [21].
  • In the second synthesis, a single mixture of four fluorous-tagged dihydroxy-tetrahydrofurans is coupled with a four-compound mixture of hydroxybutenolides that bear derivatives of DMB (dimethoxybenzyl) groups with oligoethylene glycol (OEG) units that encode the configurations at C4 and C34 [22].
  • An assay was developed to study the spontaneous transfer and transbilayer movement (flip-flop) of lipid analogs labeled with the fluorescent fatty acid, 5-(5,7-dimethyl BODIPY)-1-pentanoic acid (C5-DMB-) in large unilamellar lipid vesicles comprised of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) [23].

Regulatory relationships of HLA-DMB

  • CONCLUSION: DMA and DMB polymorphism does not seem to influence susceptibility to develop RA [11].
  • Two of these deletion mutants suppressed the activity of endogenously expressed wild-type CIITA to activate both DRA and DMB promoters [24].

Other interactions of HLA-DMB


Analytical, diagnostic and therapeutic context of HLA-DMB

  • DMA and DMB typing was achieved by PCR amplification followed by sequence-specific oligonucleotide hybridization and by PCR-restriction fragment length polymorphism [28].
  • HLA-DMB polymorphism in living-related kidney transplantation [29].
  • Immunoelectron microscopy on ultrathin cryosections showed that CD8-DMB molecules accumulated in late endocytic compartments sharing characteristics with lysosomes, like MHC class II compartments in APCs [18].
  • Coculture of strain DMA with either M. hungatei or strain DMB in solid medium with DCM as the sole added source of carbon and energy was observed [19].
  • Fiber thickness and pore size of fibrin clots, measured by permeation experiments and visualized by scanning electron microscopy, decreased significantly with DMB [21].


  1. HLA-DMA and HLA-DMB alleles in German patients with type 1 diabetes mellitus. Siegmund, T., Donner, H., Braun, J., Usadel, K.H., Badenhoop, K. Tissue Antigens (1999) [Pubmed]
  2. HLA-DMB gene and HLA-DRA promoter region polymorphisms in Australian multiple sclerosis patients. Bennetts, B.H., Teutsch, S.M., Buhler, M.M., Heard, R.N., Stewart, G.J. Hum. Immunol. (1999) [Pubmed]
  3. HLA-DMA and HLA-DMB genotyping in patients with rheumatic diseases. Yen, J.H., Tsai, W.C., Tsai, J.J., Chen, C.J., Lin, C.H., Ou, T.T., Wu, C.C., Liu, H.W. The Kaohsiung journal of medical sciences. (1999) [Pubmed]
  4. Three HLA-DMB variants in Korean patients with autoimmune diseases. Kim, T.G., Carrington, M., Choi, H.B., Kim, H.Y., Han, H. Hum. Immunol. (1996) [Pubmed]
  5. Mediation by HLA-DM of dissociation of peptides from HLA-DR. Sloan, V.S., Cameron, P., Porter, G., Gammon, M., Amaya, M., Mellins, E., Zaller, D.M. Nature (1995) [Pubmed]
  6. An essential role for HLA-DM in antigen presentation by class II major histocompatibility molecules. Morris, P., Shaman, J., Attaya, M., Amaya, M., Goodman, S., Bergman, C., Monaco, J.J., Mellins, E. Nature (1994) [Pubmed]
  7. Oxidative thymine dimer repair in the DNA helix. Dandliker, P.J., Holmlin, R.E., Barton, J.K. Science (1997) [Pubmed]
  8. Internalization and sorting of a fluorescent analogue of glucosylceramide to the Golgi apparatus of human skin fibroblasts: utilization of endocytic and nonendocytic transport mechanisms. Martin, O.C., Pagano, R.E. J. Cell Biol. (1994) [Pubmed]
  9. Conditional linkage disequilibrium analysis of a complex disease superlocus, IDDM1 in the HLA region, reveals the presence of independent modifying gene effects influencing the type 1 diabetes risk encoded by the major HLA-DQB1, -DRB1 disease loci. Zavattari, P., Lampis, R., Motzo, C., Loddo, M., Mulargia, A., Whalen, M., Maioli, M., Angius, E., Todd, J.A., Cucca, F. Hum. Mol. Genet. (2001) [Pubmed]
  10. Genomic organization of HLA-DMA and HLA-DMB. Comparison of the gene organization of all six class II families in the human major histocompatibility complex. Radley, E., Alderton, R.P., Kelly, A., Trowsdale, J., Beck, S. J. Biol. Chem. (1994) [Pubmed]
  11. HLA DRB1, DMA, and DMB gene polymorphisms in rheumatoid arthritis. Reviron, D., Tezenas du Montcel, S., Foutrier, C., Guis, S., Benazet, J.F., Auquier, P., Busson, M., Roux, H., Mercier, P., Roudier, J. Hum. Immunol. (1999) [Pubmed]
  12. HLA-DMA and HLA-DMB gene expression functions through the conserved S-X-Y region. Westerheide, S.D., Louis-Plence, P., Ping, D., He, X.F., Boss, J.M. J. Immunol. (1997) [Pubmed]
  13. HLA-DMB expression by thyrocytes: indication of the antigen-processing and possible presenting capability of thyroid cells. Wu, Z., Biro, P.A., Mirakian, R., Hammond, L., Curcio, F., Ambesi-Impiombato, F.S., Bottazzo, G.F. Clin. Exp. Immunol. (1999) [Pubmed]
  14. The DRB1 Val86/Val86 genotype associates with multiple sclerosis in Australian patients. Teutsch, S.M., Bennetts, B.H., Buhler, M.M., Heard, R.N., Stewart, G.J. Hum. Immunol. (1999) [Pubmed]
  15. Analysis of transcripts of genes located within the HLA-D region in B cells from an HLA-severe combined immunodeficiency individual. Nocera, A., Barocci, S., De Palma, R., Gorski, J. Hum. Immunol. (1993) [Pubmed]
  16. HLA-DMA and -DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells. Fling, S.P., Arp, B., Pious, D. Nature (1994) [Pubmed]
  17. Accurate intracellular localization of HLA-DM requires correct spacing of a cytoplasmic YTPL targeting motif relative to the transmembrane domain. Potter, P.K., Copier, J., Sacks, S.H., Calafat, J., Janssen, H., Neefjes, J.J., Kelly, A.P. Eur. J. Immunol. (1999) [Pubmed]
  18. Targeting signal and subcellular compartments involved in the intracellular trafficking of HLA-DMB. Copier, J., Kleijmeer, M.J., Ponnambalam, S., Oorschot, V., Potter, P., Trowsdale, J., Kelly, A. J. Immunol. (1996) [Pubmed]
  19. Dichloromethane as the sole carbon source for an acetogenic mixed culture and isolation of a fermentative, dichloromethane-degrading bacterium. Braus-Stromeyer, S.A., Hermann, R., Cook, A.M., Leisinger, T. Appl. Environ. Microbiol. (1993) [Pubmed]
  20. 'Ovar-Mhc' - ovine major histocompatibility complex: structure and gene polymorphisms. Dukkipati, V.S., Blair, H.T., Garrick, D.J., Murray, A. Genet. Mol. Res. (2006) [Pubmed]
  21. The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Standeven, K.F., Ariëns, R.A., Whitaker, P., Ashcroft, A.E., Weisel, J.W., Grant, P.J. Diabetes (2002) [Pubmed]
  22. Total synthesis of a 28-member stereoisomer library of murisolins. Curran, D.P., Zhang, Q., Richard, C., Lu, H., Gudipati, V., Wilcox, C.S. J. Am. Chem. Soc. (2006) [Pubmed]
  23. Measurement of spontaneous transfer and transbilayer movement of BODIPY-labeled lipids in lipid vesicles. Bai, J., Pagano, R.E. Biochemistry (1997) [Pubmed]
  24. Activation and transdominant suppression of MHC class II and HLA-DMB promoters by a series of C-terminal class II transactivator deletion mutants. Chin, K.C., Li, G., Ting, J.P. J. Immunol. (1997) [Pubmed]
  25. Polymorphism of the HLA-DMA and DMB genes in rheumatoid arthritis. Pinet, V., Combe, B., Avinens, O., Caillat-Zucman, S., Sany, J., Clot, J., Eliaou, J.F. Arthritis Rheum. (1997) [Pubmed]
  26. Positive association of the HLA DMB1*0101-0101 genotype with rheumatoid arthritis. Perdriger, A., Guggenbuhl, P., Chalès, G., Yaouanq, J., Quelvennec, E., Bonnard, M.N., Pawlotsky, Y., Semana, G. Rheumatology (Oxford, England) (1999) [Pubmed]
  27. HLA-DMA and HLA-DMB genotyping in patients with systemic lupus erythematosus. Yen, J.H., Chen, C.J., Tsai, W.C., Tsai, J.J., Ou, T.T., Liu, H.W. J. Rheumatol. (1999) [Pubmed]
  28. HLA DMA and DMB show no association with rheumatoid arthritis in US Caucasians. Moxley, G., Han, J. Eur. J. Immunogenet. (2001) [Pubmed]
  29. HLA-DMB polymorphism in living-related kidney transplantation. Fukuda, Y., Hoshino, S., Shintaku, S., Tanaka, I., Dohi, K., Kimura, A. Transplant. Proc. (2001) [Pubmed]
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