TCR ISOFORM CONTAINING THE FC RECEPTOR-GAMMA CHAIN EXHIBITS STRUCTURAL AND FUNCTIONAL DIFFERENCES FROM ISOFORM CONTAINING CD3-ZETA

The structure and function of the TCR-CD3 complex containing a homodim er of the gamma chain of the high affinity receptor for IgE (FcRgamma) (FcRgamma+ TCR) was investigated by transfecting the FcRgamma gene in to a CD3zeta-, CD3eta-, FcRgamma- T cell line. Introduction of FcRgamm a, as well as CD3zeta, induced a high expression of the TCR - CD3 comp lex on the cell surface. Transfected FcRgamma formed a homodimer and a ssociated firmly with the TCRalphabeta dimer but only weakly with the CD3gammadeltaepsilon. Stimulation of both FcRgamma and CD3zeta transfe ctants by antibodies against TCR or CD3 induced accumulation of inosit ol phosphates, the Ca2+ response, IL-2 production, and growth inhibiti on. On the other hand, antigen stimulation of transfectants expressing FcRgamma as well as CD3zeta induced IL-2 production, but only the lat ter exhibited the antigen-induced growth inhibition. In vitro kinase a ssay suggested that the CD3zeta dimer but not the FcRgamma dimer assoc iates with the Fyn kinase. These results indicate that the FcRgamma ho modimer is able to form a functional TCR complex but that the mode of assembly and the signaling function of FcRgamma+ TCR, including its as sociation with tyrosine kinase(s), may differ from the TCR - CD3 compl ex containing CD3zeta homodimers (zeta+ TCR). This provides an example which illustrates that different TCR isoforms mediate distinct signal s and functions.