TCR-mediated recognition of beta-linked self-glycolipids bound to CD1d is poorly understood. Here, we have characterized the TCR repertoire of a CD1d-restricted type II NKT cell subset reactive to sulfatide involved in the regulation of autoimmunity and antitumor immunity. The sulfatide/CD1d-tetramer(+) cells isolated from naïve mice show an oligoclonal TCR repertoire with predominant usage of the Valpha3/Valpha1-Jalpha7/Jalpha9 and Vbeta8.1/Vbeta3.1-Jbeta2.7 gene segments. The CDR3 regions of both the alpha- and beta-chains are encoded by either germline or nongermline gene segments of limited lengths containing several conserved residues. Presence of dominant clonotypes with limited TCR gene usage for both TCR alpha- and beta-chains in type II NKT cells reflects specific antigen recognition not found in the type I NKT cells but similar to the MHC-restricted T cells. Although potential CD1d-binding tyrosine residues in the CDR2beta region are conserved between most type I and type II NKT TCRs, CDR 1alpha and 3alpha regions differ significantly between the two subsets. Collectively, the TCR repertoire of sulfatide-reactive type II NKT cells exhibits features of both antigen-specific conventional T cells and innate-like cells, and these findings provide important clues to the recognition of beta-linked glycolipids by CD1d-restricted T cells in general.
