Requirement for the SLP-76 adaptor GADS in T cell development

GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS^- CD4^-CD8^- thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS^- thymocytes failed to respond to CD3 cross-linking in vivo and were impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS^- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling.