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 (FcR gamma) (FcR gamma+ TCR) was investigated by transfecting the FcR gamma gene into a CD3 zeta-, CD3 eta-, FcR gamma- T cell line. Introduction of FcR gamma, as well as CD3 zeta, induced a high expression of the TCR-CD3 complex on the cell surface. Transfected FcR gamma formed a homodimer and associated firmly with the TCR alpha beta dimer but only weakly with the CD3 gamma delta epsilon. Stimulation of both FcR gamma and CD3 zeta 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 FcR gamma as well as CD3 zeta induced IL-2 production, but only the latter exhibited the antigen-induced growth inhibition. In vitro kinase assay suggested that the CD3 zeta dimer but not the FcR gamma dimer associates with the Fyn kinase. These results indicate that the FcR gamma homodimer is able to form a functional TCR complex but that the mode of assembly and the signaling function of FcR gamma+ TCR, including its association with tyrosine kinase(s), may differ from the TCR-CD3 complex containing CD3 zeta homodimers (zeta+ TCR). This provides an example which illustrates that different TCR isoforms mediate distinct signals and functions.
Ohno
H
H
Division of Molecular Genetics, Chiba University, School of Medicine, Japan.
Aoe
T
T
Ra
C
C
Yamamoto
T
T
Saito
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D007295:Inositol Phosphates / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D010770:Phosphotransferases / Q000378:metabolism; D011233:Precipitin Tests; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000502:physiology; D017452:Receptors, IgG / Q000737:chemistry* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D014162:Transfection
D007295:Inositol Phosphates; D007376:Interleukin-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D017452:Receptors, IgG; D010770:Phosphotransferases; D002118:Calcium