Diverse TCRs recognize murine CD1

Human and murine T cells that specifically recognize CD1d and produce IL-4 and IFN-γ, play a role in immunoregulation and tumor rejection. In the mouse, most CD1d1-reactive T cells described express an invariant Vα14- Jα281 TCR associated with TCR β-chains of limited diversity. Similarly, human CD1d-reactive T cells express a highly restricted TCR repertoire. Here we report the unexpected result that in mice immunized with CD1d1-bearing transfectant cells, a diverse repertoire of TCRs was expressed by CD1d1- reactive T cell clones isolated by limiting dilution without preselection for NK1 expression. Only 3 of 10 CD1d1-reactive T cell clones expressed the invariant Vα14-Jα281 TCRα rearrangement. T cells expressing Vα10, -11, - 15, and -17, and having non-germline-encoded nucleotides resulting in diverse V-J junctions were identified. Like CD1d1-reactive T cells expressing the invariant Vα14-Jα281 TCR α-chain, CD1d1-reactive clones with diverse TCRs produced both Type 1 (IFN-γ) and Type 2 (IL-4, IL-10) cytokines. This establishes the existence of significant diversity in the TCRs directly reactive to the CD1d1 protein. Our findings reveal that CD1d interacts with a broad array of TCRs, suggesting substantial redundancy and flexibility of the immune system in providing T cells serving the role(s) mediated by CD1d reactivity.