Diverse TCRs recognize murine CD1

Human and murine T cells that specifically recognize CD1d and produce IL-4 and IFN-gamma play a role in immunoregulation and tumor rejection. In the m ouse, most CD1d1-reactive T cells described express an invariant V alpha 14 -J alpha 281 TCR associated with TCR beta-chains of limited diversity. Simi larly, human CD1d-reactive T cells express a highly restricted TCR repertoi re. Here we report the unexpected result that in mice immunized with CD1d1- bearing transfectant cells, a diverse repertoire of TCRs was expressed by C D1d1-reactive T cell clones isolated by limiting dilution without preselect ion for NK1 expression. Only 3 of 10 CD1d1-reactive T cell clones expressed the invariant V alpha 14-J alpha 281 TCR alpha rearrangement. T cells expr essing V alpha 10, -11, -15, and -17, and having non-germline-encoded nucle otides resulting in diverse V-J junctions were identified, Like CD1d1-react ive T cells expressing the invariant V alpha 14-J alpha 281 TCR alpha-chain , CD1d1-reactive clones with diverse TCRs produced both Type I (IFN-gamma) and Type 2 (IL-4, IL-10) cytokines, This establishes the existence of signi ficant diversity in the TCRs directly. reactive to the CD1d1 protein. Our f indings reveal that CD1d interacts with a broad array of TCRs, suggesting s ubstantial redundancy and flexibility of the immune system in providing T c ells serving the role(s) mediated by CD1d reactivity.