FUNCTIONAL CONSEQUENCES OF THE INTERACTION BETWEEN T-CELL ANTIGEN RECEPTORS AND FC-GAMMA-RS ON T-CELLS

Two series of experiments are presented indicating that Fc gamma II re ceptors can interfere with the antigen receptor-induced signaling on T cells. It has been previously described that a 13 amino acid motif on the cytoplasmic portion of Fc gamma IIB1 can abrogate the antigen rec eptor-initiated signals mediated through consensus motifs present on t he cytoplasmic portion of Ig alpha and Ig beta chains. Similar activat ing motifs are crucial to T-cell receptor (TCR) signaling. A splenic g amma/delta T-cell hybridoma that expressed the Fc gamma RII beta(1) re ceptor helped to establish that this receptor can also interfere with TCR-induced activation. The cytoplasmic portion of human Fc gamma RIIa has an activation motif similar to the activation motifs present on t he TCR. Using a transgenic mouse in which the T cells express the huma n Fc gamma RIIa transgene, we demonstrated that despite the common act ivation motif, the TCR and human Fc gamma RIIa-induced signals are dif ferent. Additionally, the human Fc gamma RIIa expressing T cells exhib it an enhanced TCR response both in vitro and in vivo.