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 phenyla lanine (phe(195)) in the Tcr-C alpha region on Tcr-alpha/beta/CD3 memb rane expression. An exchange of phe(195) with a tyrosine residue does not affect Tcr/CD3 membrane expression; however, exchange with asparti c acid, histidine or valine prohibit completely Tcr/CD3 membrane expre ssion. This seems to be due to a lack of interaction between mutated T cr-alpha,beta/CD3-gamma epsilon,delta epsilon complexes and zeta(2) ho modimers. The Tcr-C alpha region around phe(195) seems together with t he same region in the Tcr-C beta region to constitute an interaction s ite for zeta(2) homodimers. The presence of phe(195) on both Tcr-C alp ha and Tcr-C beta causes high avidity interaction with zeta 2 homodime rs, whereas his(195) in both Tcr-C gamma and Tcr-C delta results in an apparently lower avidity interaction with zeta(2) homodimers. It is s uggested that the phe(195) region (on beta-strand F) and eventually ad jacent aromatic amino acid residues on beta-strand B region may play a n important role in Tcr-alpha,beta/CD3 membrane expression, in Tcr-alp ha,beta/CD3 competition with Tcr-gamma,delta/CD3 complexes for zeta 2 homodimers and in the control of formation of 'mixed' Tcr heterodimers .