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A NK1.1⁺ Thymocyte-Derived TCR ß-Chain Transgene Promotes Positive Selection of Thymic NK1.1⁺ ß T Cells¹

Christophe Viret^*, Olivier Lantz, Xin He^*, Albert Bendelac and Charles A. Janeway, Jr.^2,3,*

^* Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520; Institut National de la Santé et de la Recherche Médicale, Unité 25, Hopital Necker, Paris, France; and Department of Molecular Biology, Princeton University, Princeton, NJ 08540

As a consequence of the peptide specificity of intrathymic positive selection, mice transgenic for a rearranged TCR ß-chain derived from conventional ß T lymphocytes frequently carry mature T cells with significant skewing in the repertoire of the companion -chain. To assess the generality of such an influence, we generated transgenic (Tg) mice expressing a ß-chain derived from nonclassical, NK1.1⁺ ß T cells, the thymus-derived, CD1.1-specific DN32H6 T cell hybridoma. Results of the sequence analysis of genomic DNA from developing DN32H6 ß Tg thymocytes revealed that the frequency of the parental -chain sequence, in this instance the V14-J281 canonical -chain, is specifically and in a CD1.1-dependent manner, increased in the postselection thymocyte population. In accordance, we found phenotypic and functional evidence for an increased frequency of thymic, but interestingly not peripheral, NK1.1⁺ ß T cells in DN32H6 ß Tg mice, possibly indicating a thymic determinant-dependent maintenance. Thus, in vivo expression of the rearranged TCR ß-chain from a thymus-derived NK1.1⁺ V14⁺ T cell hybridoma promotes positive selection of thymic NK1.1⁺ ß T cells. These observations indicate that the strong influence of productive ß-chain rearrangements on the TCR sequence and specificity of developing thymocytes, which operates through positive selection on self-determinants, applies to both classical and nonclassical ß T cells and therefore represents a general phenomenon in intrathymic ß T lymphocyte development.