A highly conserved phenylalanine in the alpha, beta-T cell receptor (TCR) constant region determines the integrity of TCR/CD3 complexes.

In the present study, we have investigated the importance of a phenylalanine (phe195) in the Tcr-C alpha region on Tcr-alpha,beta/CD3 membrane expression. An exchange of phe195 with a tyrosine residue does not affect Tcr/CD3 membrane expression; however, exchange with aspartic acid, histidine or valine prohibit completely Tcr/CD3 membrane expression. This seems to be due to a lack of interaction between mutated Tcr-alpha,beta/CD3-gamma epsilon,delta epsilon complexes and zeta 2 homodimers. The Tcr-C alpha region around phe195 seems together with the same region in the Tcr-C beta region to constitute an interaction site for zeta 2 homodimers. The presence of phe195 on both Tcr-C alpha and Tcr-C beta causes high avidity interaction with zeta 2 homodimers, whereas his195 in both Tcr-C gamma and Tcr-C delta results in an apparently lower avidity interaction with zeta 2 homodimers. It is suggested that the phe195 region (on beta-strand F) and eventually adjacent aromatic amino acid residues on beta-strand B region may play an important role in Tcr-alpha,beta/CD3 membrane expression, in Tcr-alpha,beta/CD3 competition with Tcr-gamma,delta/CD3 complexes for zeta 2 homodimers and in the control of formation of 'mixed' Tcr heterodimers.