HLA-DMB explained

HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.^{[1] [2]}

Function

HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26–28 kDa and its gene contains 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.^[2]

Clinical significance

HLA-DMB is upregulated in tumor tissue of Caucasian but not African patients. Its role in tumor immunology is undefined but has been shown to positively correlated with increased T-cell infiltration and improved prognosis in ovarian cancer. Differential immune processes mediated by HLA-DMB may contribute to the disparity in cancer outcome.^[3]

Further reading

• Vogt AB, Kropshofer H . HLA-DM - an endosomal and lysosomal chaperone for the immune system. . Trends Biochem. Sci. . 24 . 4 . 150–4 . 1999 . 10322421 . 10.1016/S0968-0004(99)01364-X .
• Kropshofer H, Hämmerling GJ, Vogt AB . The impact of the non-classical MHC proteins HLA-DM and HLA-DO on loading of MHC class II molecules. . Immunol. Rev. . 172 . 267–78 . 2000 . 10631952 . 10.1111/j.1600-065X.1999.tb01371.x . 22216172 .
• 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 .
• 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 .
• 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 .
• 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 .
• 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 .
• Andrieu JM, Even P, Venet A . AIDS and related syndromes as a viral-induced autoimmune disease of the immune system: an anti-MHC II disorder. Therapeutic implications. . AIDS Research . 2 . 3 . 163–74 . 1986 . 3489470 . 10.1089/aid.1.1986.2.163.
• Houlgatte R, Scarmato P, el Marhomy S, etal . HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4. . J. Immunol. . 152 . 9 . 4475–88 . 1994 . 10.4049/jimmunol.152.9.4475 . 7512597 . free .
• Shaman J, von Scheven E, Morris P, etal . Analysis of HLA-DMB mutants and -DMB genomic structure. . Immunogenetics . 41 . 2–3 . 117–24 . 1995 . 7528727 . 10.1007/BF00182322 . 40078535 .
• Chirmule N, McCloskey TW, Hu R, etal . HIV gp120 inhibits T cell activation by interfering with expression of costimulatory molecules CD40 ligand and CD80 (B71) . J. Immunol. . 155 . 2 . 917–24 . 1995 . 10.4049/jimmunol.155.2.917 . 7541827 . free .
• Rowell JF, Stanhope PE, Siliciano RF . Endocytosis of endogenously synthesized HIV-1 envelope protein. Mechanism and role in processing for association with class II MHC . J. Immunol. . 155 . 1 . 473–88 . 1995 . 10.4049/jimmunol.155.1.473 . 7602119 . 19994352 .
• Sherman MA, Weber DA, Jensen PE . DM enhances peptide binding to class II MHC by release of invariant chain-derived peptide . Immunity . 3 . 2 . 197–205 . 1995 . 7648393 . 10.1016/1074-7613(95)90089-6 . free .
• Radley E, Alderton RP, Kelly A, etal . 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 . J. Biol. Chem. . 269 . 29 . 18834–8 . 1994 . 10.1016/S0021-9258(17)32242-1 . 8034636 . free .
• Chen YH, Böck G, Vornhagen R, etal . HIV-1 gp41 binding proteins and antibodies to gp41 could inhibit enhancement of human Raji cell MHC class I and II expression by gp41 . Mol. Immunol. . 31 . 13 . 977–82 . 1994 . 8084338 . 10.1016/0161-5890(94)90092-2 .
• Fling SP, Arp B, Pious D . HLA-DMA and -DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells . Nature . 368 . 6471 . 554–8 . 1994 . 8139690 . 10.1038/368554a0 . 1994Natur.368..554F . 4307699 .
• Chirmule N, Wang XP, Hu R, etal . Envelope glycoproteins of HIV-1 interfere with T-cell-dependent B cell differentiation: role of CD4-MHC class II interaction in the effector phase of T cell help . Cell. Immunol. . 155 . 1 . 169–82 . 1994 . 8168144 . 10.1006/cimm.1994.1110 . free .
• Sanderson F, Powis SH, Kelly AP, Trowsdale J . Limited polymorphism in HLA-DM does not involve the peptide binding groove . Immunogenetics . 39 . 1 . 56–8 . 1993 . 8225438 . 10.1007/bf00171797. 27369392 .
• Callahan KM, Rowell JF, Soloski MJ, etal . HIV-1 envelope protein is expressed on the surface of infected cells before its processing and presentation to class II-restricted T lymphocytes . J. Immunol. . 151 . 6 . 2928–42 . 1993 . 10.4049/jimmunol.151.6.2928 . 8376762 . free .

Notes and References

1. Kelly AP, Monaco JJ, Cho SG, Trowsdale J . A new human HLA class II-related locus, DM . Nature . 353 . 6344 . 571–3 . Nov 1991 . 1922365 . 10.1038/353571a0 . 1991Natur.353..571K . 3065226 .
2. Web site: Entrez Gene: HLA-DMB major histocompatibility complex, class II, DM beta.
3. Kinseth MA, Jia Z, Rahmatpanah F, Sawyers A, Sutton M, Wang-Rodriguez J, Mercola D, McGuire KL . Expression differences between African American and Caucasian prostate cancer tissue reveals that stroma is the site of aggressive changes. . International Journal of Cancer. 134 . 1 . 81–91 . Jan 2014 . 23754304 . 3800217. 10.1002/ijc.28326 .