TCR isoform containing the Fc receptor ? chain exhibits structural and functional differences from isoform containing CD3?

Abstract

The structure and function of the TCR-CD3 complex containing a homodimer of the gamma chain of the high affinity receptor for IgE (FcR_γ) (FcR_γ⁺ TCR) was investigated by transfecting the FcR_γ gene into a CD3ξ⁻, CD3η⁻, FcR_γ⁻ T cell line. Introduction of FcR_γ, as well as CD3ξ, induced a high expression of the TCR-CD3 complex on the cell surface. Transfected FCR_γ formed a homodimer and associated firmly with the TCRαβ dimer but only weakly with the CD3_γδ_ε. Stimulation of both FcR_γ and CD3ξ 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_γ as well as CD3ξ induced IL-2 production, but only the latter exhibited the antigen-induced growth inhibition. In vitro kinase assay suggested that the CD3ξ dimer but not the FcR_γ dimer associates with the Fyn kinase. These results indicate that the FcR_γ homodlmer Is able to form a functional TCR complex but that the mode of assembly and the signaling function of FcR_γ⁺ TCR, including its association with tyrosine klnase(s), may differ from the TCR-CD3 complex containing CD3ξ homodimers (ξ⁺ TCR). This provides an example which illustrates that different TCR isoforms mediate distinct signals and functions.