HLA-DMA and -DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells.
Major histocompatibility complex (MHC) class II molecules are highly polymorphic cell-surface glycoproteins that present antigenic peptides to CD4+ T lymphocytes. The normal assembly of class II molecules with cognate peptides for antigen presentation requires an accessory function provided by a gene mapping to the class II region of the HLA complex. The isolation of somatic cell mutants of antigen-presenting cells (APC) has shown that at least one gene which maps between HLA-DP and HLA-DQ, provisionally designated c2p-1 (ref. 3), mediates this process. Here we describe a unique new mutant 2.2.93, which manifests defective formation of class II/peptide complexes like that described in c2p-1 mutants. We show that (1) mutant 2.2.93 contains a mutation in HLA-DMA, and a representative c2p-1 mutant, 9.5.3, contains a mutation in HLA-DMB; and (2) transfection and expression of DMA complementary DNA in 2.2.93, and DMB cDNA in 9.5.3, reverses their mutant phenotypes. These results show that HLA-DMA and -DMB, genes of previously unknown function mapping between HLA-DP and HLA-DQ, are required for the normal assembly of peptides with MHC class II molecules. They suggest that HLA-DMA and -DMB encode subunits of a functional heterodimer which is critical in the pathway of class II antigen presentation.
Fling
S P
SP
Department of Pediatrics, University of Washington, Seattle 98195.
Arp
B
B
Pious
D
D
D000938:Antigen-Presenting Cells / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D018076:DNA, Complementary; D006681:HLA-D Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II