Innate immune functions of human gamma-delta T lymphocytes

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T lymphocytes expressing the ab T-cell receptor (TCR) display a broad diversity of TCR germline repertoire, recognize antigen-derived peptides in an MHC class I or class II-restricted manner, and are effector cells of the adaptive cellular immune system. In striking contrast, T lymphocytes expressing the alternative gd TCR have a very restricted TCR germline repertoire, and characteristically recognize phosphorylated intermediates of the bacterial isoprenoid biosynthesis pathway in a non-MHC-restricted and antigen presentation-independent fashion. Thus, it appears that human gd T cells use their TCR as a pattern recognition receptor for the rapid recognition of microbial products that are not seen by other cells of the innate or adaptive immune system. The present proposal will focus on two major goals: (i) To characterize in detail the rapid response of human gd T cells to bacterial phosphoantigens at the level of effector functions (e.g., cytokine production) and signal transduction pathways; and (ii) to investigate in detail the expression and possible function of toll-like receptors (TLR), an additional set of pattern recognition receptors of innate immune cells, on human gd T lymphocytes. These studies will help to clarify the role of human gd T cells as a potential link between the innate and the adaptive immune system.