Absolute requirement for the pre-T cell receptor alpha chain during NK1.1(+)TCR alpha beta cell development

Most natural killer T (NKT) cells express a highly skewed alpha beta TCR re pertoire, consisting of an invariant V alpha 14-J alpha 281 chain paired pr eferentially with a polyclonal V beta 8.2 chain. This repertoire is positiv ely selected by the monomorphic CD1d molecule expressed on cells of hematop oietic origin. The origin of NKT cells and their lineage relationship to co nventional T cells is controversial. We show here that the development of N KT cells is absolutely dependent on expression of the pre-TCR alpha chain, in marked contrast to conventional T cells which arise in significant numbe rs even in the absence of a functional pre-TCR. Distinct developmental requ irements for pre-TCR expression in the NKT and T cell lineages may reflect differences in the ability of the TCR alpha beta to substitute functionally for the pre-TCR in immature precursor cells.