TCRgamma delta cells are distinct from TCRalpha beta cells based on their tissue distribution and antigen recognition. In this regard very little is known about the biochemical and molecular mechanism of TCRgamma delta cell activation. T cell activation depends on antigen recognition by two clonally distributed chains, alpha beta or gamma delta, and the CD3 invariant chains gamma delta and epsilon and zetu-zetu or zetu-eta dimers. The zetu-chains are the major transducing elements of activation signals initiated upon ligand binding by the TCR. We and others have shown that TCRgamma delta cells express a distinct member of the zetu family, the delta chain of FcepsilonRI (FcepsilonRIgamma). Whereas several studies have shown that the zetu-chain couples the TCR to intracellular protein tyrosine kinases (PTK), the role of FcepsilonRIgamma chain in TCR function remains unclear. We have developed a model system to study the role of FcepsilonRIgamma chain in gamma delta T cell receptor function, utilizing a TCRgamma delta transgenic mice crossed with CD3zetu chain deficient mice. These mice will be reconstituted with FcepsilonRIgamma, TCRzetu or chimeras of FcepsilonRIgamma/TCRzetu chains, and used to evaluate whether the FcepsilonRIgamma chain is able to replace the zetu chain in the developmental process, cell surface trafficking and functional responses of the TCR. In addition, the PTK that associate with the receptor and the intracellular signalling events following the T cell activation will also be studied.
