Signaling efficiency of the T cell receptor controlled by a single amino acid in the beta chain constant region

A single amino acid residue, Gln(136), located within the connecting peptide domain of C beta controls the ability of the alpha/beta TCR to transmit a full signal. TCRs in which this CP residue is mutated to Phe, the residue found in TCR-gamma, are unresponsive to antigenic ligands. Interestingly, this C beta residue is either polar or charged in every species studied thus far, including the trout and the skate. In contrast, the analogous residue in C gamma is always hydrophobic. In spite of their compromised antigen responsiveness, the mutant TCR complex contains the CD3-gamma, -delta, -epsilon, and -zeta; chains, and undergoes zeta chain phosphorylation and ZAP-70 recruitment. However, the biological response of the mutant TCR could be rescued with a calcium ionophore, implying that mutant TCRs are defective in generating a calcium-mediated signal. The implications of the differences between C beta and C gamma are considered.