Transmembrane polar residues of TCR β chain are required for signal transduction

Mutagenic analyses have identified structural motifs important for TCR-mediated signaling in the antigen-binding chains, CD3 and ζ subunits of the TCR complex. In this study, we altered selected residues in the transmembrane and extracellular constant regions of the TCR β chain and expressed the mutants in a T hybridoma line bearing endogenous receptor. We measured cytokine production and apoptosis in response to antigen or antibody. We found that mutation of one or both of the transmembrane tyrosine residues in the TCR β chain caused a marked reduction in responsiveness. Mutation of the transmembrane serine to alanine also reduced responses, although less markedly. Immunoprecipitation analyses showed that the TCR β mutations did not alter association with ζ. These experiments identify a signaling role for the transmembrane domain of the TCR β chain.