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.
Caspar-Bauguil
S
S
Immunopathology and Human Genetics Center (CIGH), Toulouse, France.
Arnaud
J
J
Huchenq
A
A
Hein
W R
WR
Geisler
C
C
Rubin
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D017252:CD3 Complex / Q000096:biosynthesis*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000502:physiology*; D017354:Point Mutation; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D018076:DNA, Complementary; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D010649:Phenylalanine