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 homodimer of the gamma chain of the high affinity receptor for IgE (FcRgamma) (FcRgamma+ TCR) was investigated by transfecting the FcRgamma gene into a CD3zeta-, CD3eta-, FcRgamma- T cell line. Introduction of FcRgamma, as well as CD3zeta, induced a high expression of the TCR - CD3 complex on the cell surface. Transfected FcRgamma formed a homodimer and associated firmly with the TCRalphabeta dimer but only weakly with the CD3gammadeltaepsilon. Stimulation of both FcRgamma and CD3zeta transfectants by antibodies against TCR or CD3 induced accumulation of inositol phosphates, the Ca2+ response, IL-2 production, and growth inhibition. On the other hand, antigen stimulation of transfectants expressing FcRgamma as well as CD3zeta induced IL-2 production, but only the latter exhibited the antigen-induced growth inhibition. In vitro kinase assay suggested that the CD3zeta dimer but not the FcRgamma dimer associates with the Fyn kinase. These results indicate that the FcRgamma homodimer is able to form a functional TCR complex but that the mode of assembly and the signaling function of FcRgamma+ TCR, including its association with tyrosine kinase(s), may differ from the TCR - CD3 complex containing CD3zeta homodimers (zeta+ TCR). This provides an example which illustrates that different TCR isoforms mediate distinct signals and functions.