In T cells of patients with systemic lupus erythematosus (SLE) high level expression of Fc epsilon RI gamma chain replaces the deficient TCR zeta-chain and contributes to altered TCR/CD3-mediated signaling abnormalities. Fc epsilon RI gamma mediates signaling by associating with the structurally homologous tyrosine phosphorylated protein kinase, Syk. In this study, the authors directly tested whether forced expression of Fc epsilon RI gamma chain in normal T cells, which do not express this molecule, would lead to increased T cell responsiveness similar to that observed in SLE T cells. Primary T cells nucleofected with an expression vector encoding Fc epsilon RI gamma showed a co-localization of Fc epsilon RI gamma with CD3epsilon. In addition, Fc epsilon RI gamma overexpression leads to an up-regulation of TCR/CD3 mediated tyrosine phosphorylation of cellular substrates and protein kinase Syk.