TCR-GAMMA-DELTA CELLS IN CD3-ZETA-DEFICIENT MICE CONTAIN FC-EPSILON-RI-GAMMA IN THE RECEPTOR COMPLEX BUT ARE SPECIFICALLY UNRESPONSIVE TO ANTIGEN

Unlike TCR-alpha beta cells, TCR-gamma delta cells express a distinct member of the zeta family, the gamma-chain of Fc epsilon RI (Fc epsilo n RI gamma) within the TCR complex. To study the role of the Fc epsilo n RI gamma-chain in TCR-gamma delta cells, a TCR-gamma delta transgeni c mouse (G8) has been crossed with CD3 zeta-chain-deficient mice (G8.z eta(-/-)). Thy-1(+) spleen and lymph node cells of these animals expre ssed low levels of CD3/TCR, These results suggested that the zeta-chai n is required for effective TCR transport to the cell surface. In cont rast, intraepithelial TCR-gamma delta cells of G8.zeta(-/-) mice expre ssed high levels of TCR. Immunoprecipitation with anti-CDS showed that Fc epsilon RI gamma-chains were associated with the TCR complex in T cells isolated from zeta-deficient mice, Although the Fc epsilon RI ga mma-expressing T cells proliferated in response to stimulation by TCR- specific Abs including anti-CD3 epsilon, anti-pan gamma delta, and ant i-V gamma 2 mAb, the G8.zeta(-/-) T cells did not respond to the G8-sp ecific Ag(T10(b)), anti-Thy-1 mAb, or Con A, The unresponsiveness to t he Ag was not due to the reduced TCR expression, because intraepitheli al TCR-gamma delta cells from the zeta-deficient mice did not respond to Ag. The inability of the G8.zeta(-/-) T cells to respond to Ag coul d not be overcome by providing an anti-CD28 costimulatory signal or by adding exogenous rIL-2, Taken together, our data suggest that the Fc epsilon RI gamma-chain associates with the TCR-gamma delta complex in the absence of the zeta-chain, but it is not able to substitute for th e zeta-chain for effective transport of TCR to the cell surface or fun ctional responses to Ag.