T-cell receptor alpha-chain variable-region haplotypes of normal and autoimmune laboratory mouse strains.
We used Southern blotting and mRNA analysis to characterize allelic polymorphisms among genes of the T-cell antigen receptor (TCR) alpha-chain variable-region (V alpha) locus in a large panel of normal and autoimmune-susceptible or autoimmune-contributing strains of laboratory mice. Four major V alpha haplotypes were defined on the basis of multiple restriction fragment length polymorphisms for each of nine V alpha subfamily probes used. Southern blotting also revealed haplotype-specific loss of bands within some V alpha subfamilies, consistent with the deletion of particular V alpha genes or sets of genes from haplotype to haplotype. In contrast to the situation in the V beta locus, however, deletion of entire V alpha subfamilies was not observed. The nature of V alpha allelic variability was further explored by using an RNase protection assay to analyze expressed V alpha mRNA sequences in thymocyte RNA. Such analysis revealed both shared and unique patterns of V alpha mRNA expression among the different haplotypes and supported the conclusion that haplotype differences sometimes involve V alpha gene deletions. Interestingly, a disproportionate number of, but not all, autoimmune-susceptible strains, including NZB, SJL, SWR, PL/J, and NOD, share a common V alpha haplotype. The identification of murine TCR V alpha haplotypes should provide a basis for understanding the role of TCR diversity in normal immunoregulatory and immune-response phenomena, as well as autoimmune-disease predisposition.
D000483:Alleles; D000818:Animals; D001323:Autoantibodies / Q000235:genetics*; D015139:Blotting, Southern; D004247:DNA / Q000032:analysis; D006239:Haplotypes; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000032:analysis*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
D001323:Autoantibodies; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D004247:DNA