CD1d-specific NK1.1(+) T cells with a transgenic variant TCR

The majority of T lymphocytes carrying the NK cell marker NK1.1 (NKT cells) depend on the CD1d molecule for their development and are distinguished by their potent capacity to rapidly secrete cytokines upon activation. A subs tantial fraction of NKT cells express a restricted TCR repertiore using an invariant TCR V alpha 14-J alpha 281 rearrangement and a limited set of TCR V beta segments, implying recognition of a limited set of CD1d-associated ligands. A second group of CD1d-reactive T cells use diverse TCR potentiall y recognizing a larger diversity of ligands presented on CD1d. In TCR-trans genic mice carrying rearranged TCR genes from a CD1d-reactive T cell with t he diverse type receptor (using V alpha 3.2/V beta 9 rearrangements), the m ajority of T cells expressing the transgenic TCR had the typical phenotype of NKT cells. They expressed NK1.1, CD122, intermediate TCR levels, and mar kers indicating previous activation and were CD4/CD8 double negative or CD4 (+). Upon activation in vitro, the cells secreted large amounts of IL-4 and IFN-gamma, a characteristic of NKT cells. In mice lacking CD1d, TCR-transg enic cells with the NKT phenotype were absent. This demonstrates that a CD1 d-reactive TCR of the "non-V alpha 14" diverse type can, in a ligand-depend ent way, direct development of NK1.1(+) T cells expressing expected functio nal and cell-surface phenotype characteristics.