title: Gene conversion between murine class II major histocompatibility complex loci. Functional and molecular evidence from the bm 12 mutant.
abstract: The experiments presented in this study define the molecular basis of the bm 12 mutation. Initial characterization of an alloreactive T cell clone, 4.1.4, showed this clone to recognize an allodeterminant present on the E beta b and A beta bm12 chains, but not on the bm 12 parent A beta b chain. To define the extent of sequence shared between the I-E beta product and the mutant I-A beta product, we isolated a cDNA clone of the E beta b gene and determined its nucleotide sequence. Comparison of the nucleotide sequences of E beta b, A beta b, and A beta bm12 shows the the A beta bm12 gene to be identical to the E beta b gene in the region where it differs from its A beta b parent. We predict that the bm 12 mutation arose by gene conversion of this region, which spans 14 nucleotides between amino acid residues 67-71 of the mature A beta chain, from the E beta b locus to the corresponding position at the A beta b locus. Recognition of this region, which spans one of the previously defined E beta allelic "hypervariable" regions, by an alloreactive T cell clone provides the first direct evidence of the functional importance of these hypervariable regions in T cell stimulation. The identification of a gene conversion event involving one of these allelic variable regions implicates conversion as a mechanism that acts on class II beta genes to create sequence diversity in regions of Ia molecules that interact with foreign antigen or a T cell receptor, regions where protein sequence polymorphism would presumably be selected for by the expanded ability it affords the organism to mount effective immune responses against a wider variety of foreign antigens.
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D001483:Base Sequence; D001667:Binding, Competitive; D002469:Cell Separation; D002999:Clone Cells / Q000276:immunology; D005260:Female; D005785:Gene Conversion; D005802:Genes, MHC Class II; D006649:Histocompatibility Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen