T-cell receptor alpha-chain variable-region haplotypes of normal and autoimmune laboratory mouse strains.

Abstract

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.