Selective decreases in T cell receptor V beta expression. Decreased expression of specific V beta families is associated with expression of multiple MHC and non-MHC gene products

摘要

Previous reports of TCR V beta usage, studying either expression of a single V beta in a wide panel of strains (6, 7, 10, 12, 13), or expression of multiple V beta s in a very limited strain distribution (14, 15), have identified instances of clonal deletion of potentially autoreactive T cells specific for either self E alpha E beta or minor lymphocyte stimulatory (Mls) antigens. The present study has investigated the range of self antigens that can influence V beta usage by evaluating expression of 16 V beta families in 30 strains of mice. It was found that significant decreases in expression occur in at least 8 of the 16 V beta families and that dominant influences on the T cell V beta repertoire are exerted by expression of Mlsa, Mlsc, and MHC gene products. Decreased expressions of V beta 5, -11, -12, and -16 were influenced by MHC gene products. The patterns of decreased expression seen in intra-MHC recombinant strains and strains of different non-MHC background were distinct for V beta 11, -12, and -16, suggesting that different ligands are involved in the deletion of T cells expressing each of these V beta genes. Mice expressing Mlsa show decreased expression of V beta 9 as well as V beta 6. Mlsc mice lacked V beta 3 expression in those strains where the expressed MHC type was compatible with a strongly stimulatory Mlsc phenotype. V beta 7 was strongly influenced by both MHC and non-MHC products that are not yet identified. These results demonstrate that strain-specific decreases of mRNA expression occur in a major portion of the TCR repertoire. Self antigens including Mlsa, Mlsc, and E alpha E beta, as well as additional MHC and non-MHC products, appear to induce these decreases in expression in the process of eliminating self-reactive T cells from the mature T cell pool.