Alternative titles; symbols
HGNC Approved Gene Symbol: HLA-DMA
Cytogenetic location: 6p21.32 Genomic coordinates (GRCh38): 6:32,948,618-32,953,097 (from NCBI)
Kelly et al. (1991) isolated 2 new class II-like cDNAs, RING6 and RING7 (HLA-DMB; 142856). The structure of the genes indicated that they are novel members of the immunoglobulin gene family, which may have diverged before the duplications that gave rise to the main class II loci. Kelly et al. (1991) concluded that the RING6 and RING7 genes encode the alpha- and beta-chains of a previously undiscovered class II-related protein. The genes are highly conserved between human and mouse (Cho et al., 1991).
On the basis of genomic nucleotide sequencing of HLA-DMA and HLA-DMB and comparison of their gene organizations with other class II genes, Radley et al. (1994) concluded that all alpha genes are composed of 5 exons and all beta genes of 6 exons, and that the intron/exon boundary classes of exons 1-4 in alpha genes and exons 1-5 in beta genes are 100% conserved. Only the last boundary class, which falls within the cytoplasmic domain, appears to be variable. Sequence differences of DMA and DMB suggested that they originated before divergence of the main class II genes.
Kelly et al. (1991) identified the HLA-DMA gene in the MHC class II region on chromosome 6p21.3. Using restriction analysis, they demonstrated that HLA-DMA and HLA-DMB map between HLA-DN-alpha (142930) and HLA-DO-beta (142940).
Morris et al. (1994) and Fling et al. (1994) demonstrated that the HLA-DMA and HLA-DMB genes map between HLA-DP (142880) and HLA-DQ (146880) on chromosome 6p21.3. The mapping was achieved by study of MHC deletion mutants (Kelly et al., 1991).
Morris et al. (1994) and Fling et al. (1994) presented results based on mutation analyses indicating that the HLA-DMA and HLA-DMB genes are required for the normal assembly of peptides with MHC class II molecules. They suggested that HLA-DMA and -DMB encode subunits of a functional heterodimer that is critical in the pathway of class II antigen presentation.
Weber et al. (1996) analyzed the function of HLA-DM in antigen presentation. They reported that HLA-DM plays a critical role in catalyzing the release of Class II HLA-associated invariant chain-derived peptides (CLIP) from newly synthesized class II HLA molecules and freeing the peptide binding site for acquisition of antigenic peptides. They noted that DM-deficient antigen presenting cells are defective in presentation of protein antigens to T cells and that the class II molecules expressed in these cells are largely occupied by a nested set of CLIP peptides that share a core sequence.
Cho, S., Attaya, M., Monaco, J. J. New class II-like genes in the murine MHC. Nature 353: 573-576, 1991. [PubMed: 1922366] [Full Text: https://doi.org/10.1038/353573a0]
Fling, S. P., 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: 554-558, 1994. [PubMed: 8139690] [Full Text: https://doi.org/10.1038/368554a0]
Kelly, A. P., Monaco, J. J., Cho, S., Trowsdale, J. A new human HLA class II-related locus, DM. Nature 353: 571-573, 1991. [PubMed: 1922365] [Full Text: https://doi.org/10.1038/353571a0]
Morris, P., Shaman, J., Attaya, M., Amaya, M., Goodman, S., Bergman, C., Monaco, J. J., Mellins, E. An essential role for HLA-DM in antigen presentation by class II major histocompatibility molecules. Nature 368: 551-554, 1994. [PubMed: 8139689] [Full Text: https://doi.org/10.1038/368551a0]
Radley, E., Alderton, R. P., Kelly, A., Trowsdale, J., Beck, S. Genomic organization of HLA-DMA and HLA-DMB: comparison of the gene organization of all 6 class II families in the human histocompatibility complex. J. Biol. Chem. 269: 18834-18838, 1994. [PubMed: 8034636]
Weber, D. A., Evavold, B. D., Jensen, P. E. Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM. Science 274: 618-620, 1996. [PubMed: 8849454] [Full Text: https://doi.org/10.1126/science.274.5287.618]