CD1 restricted recognition by murine T cells.

Abstract

CD1 molecules are non-polymorphic glycoproteins distantly related to major histocompatibility complex (MHC) molecules and represent a third lineage of antigen-presenting molecules in the immune system. An unusual subset of CD1d restricted T cells in mice called NK T cells, express an invariant Valpha14-Jalpha281 T cell receptor (TCR)alpha rearrangement. NK T cells have been shown to play a pivotal role in the regulation of the immune response, the development of autoimmunity and in tumour rejection. By immunizing mice with CD1d expressing transfectant cells, a panel of CD1d restricted, directly reactive T cell clones was generated. Functionally similar to NK T cells, these T cell clones secreted both Type1 (IFN-gamma) and Type 2 (IL-4, IL-10) cytokines upon stimulation. In contrast, detailed TCR analysis revealed that a diverse repertoire of T cells could recognize CD1d. T cells expressing Valpha10, -11, -15 and -17 and having non-germline-encoded nucleotides resulting in diverse V-J junctions were identified. Three clones expressed the invariant Valpha14-Jalpha281 TCR but were functionally indistinguishable from the clones expressing diverse TCRs. Murine gammadelta T cells were examined for similar reactivity to CD1d, but specific recognition of CD1d could not be demonstrated. These data establish that the universe of TCRs capable of direct recognition of CD1d is more diverse than was previously appreciated, indicating the flexibility of the adaptive immune system in response to CD1d mediated processes. (Abstract shortened by UMI.)