A NK1.1(+) thymocyte-derived TCR beta-chain transgene promotes positive selection of thymic NK1.1(+) alpha beta T cells

As a consequence of the peptide specificity of intrathymic positive selecti on, mice transgenic for a rearranged TCR beta -chain derived from conventio nal alpha beta T lymphocytes frequently carry mature T cells with significa nt skewing in the repertoire of the companion alpha -chain, To assess the g enerality of such an influence, we generated transgenic (Tg) mice expressin g a beta -chain derived from nonclassical, NK1.1(+) alpha beta T cells, the thymus-derived, CD1.1-specific DN32H6 T cell hybridoma, Results of the seq uence analysis of genomic DNA from developing DN32H6 beta Tg thymocytes rev ealed that the frequency of the parental cy-chain sequence, in this instanc e the V alpha 14-J alpha 281 canonical alpha -chain, is specifically and in a CD1.1-dependent manner, increased in the postselection thymocyte populat ion, In accordance, we found phenotypic and functional evidence for an incr eased frequency of thymic, but interestingly not peripheral, NK1.1(+) alpha beta T cells in DN32H6 beta Tg mice, possibly indicating a thymic determin ant-dependent maintenance. Thus, in vivo expression of the rearranged TCR b eta -chain from a thymus-derived NK1.1(+) V alpha 14(+) T cell hybridoma pr omotes positive selection of thymic NK1.1(+) alpha beta T cells. These obse rvations indicate that the strong influence of productive beta -chain rearr angements on the TCR sequence and specificity of developing thymocytes, whi ch operates through positive selection on self-determinants, applies to bot h classical and nonclassical alpha beta T cells and therefore represents a general phenomenon in intrathymic alpha beta T lymphocyte development.