The implications of subunit interactions for the structure of the T cell receptor-CD3 complex.
Cell surface-expressed receptors are often multichain complexes. One of these, the T cell receptor (TcR) alpha/beta-CD3 complex, is known to contain at least seven chains: the alpha and beta TcR chains plus the gamma, delta, epsilon and two zeta chains from the CD3 complex (alpha beta gamma delta epsilon zeta 2). To gain insight into the structure of the complex we have used anti-peptide antisera specific for the individual subunits of the complex, and nonionic and ionic detergents to determine subunit interactions within the complex. Four closely associated pairs of chains could be identified: alpha beta, zeta 2, gamma epsilon and delta epsilon. Interactions between the TcR alpha beta and either gamma epsilon or delta epsilon could be observed in the apparent absence of other CD3 chains. Furthermore, a hierarchy in the strength of the association between the TcR and the individual CD3 chains could be distinguished: TcR epsilon greater than TcR delta greater than TcR gamma. The zeta 2 dimer could only be detected in "intact" TcR-CD3 complexes shedding no light on possible interactions with either the TcR or CD3-gamma, delta and epsilon chains. Finally, cross-linking experiments suggest a close spatial relationship between the TcR alpha beta and both the CD3-gamma and CD3-epsilon chains. The results demonstrate that the methods used give valuable information on subunit interactions in a cell surface-expressed receptor complex and suggest a TcR-CD3 complex in which two epsilon chains are present, one linked to gamma and the other to delta. The data further indicate that gamma epsilon and delta epsilon complexes interact directly with the TcR chains. Based on the observations a model for the structure of the TcR-CD3 is presented and discussed.
Koning
F
F
Department of Immunohematology, University Hospital, Leiden, The Netherlands.
Maloy
W L
WL
Coligan
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017252:CD3 Complex; D002462:Cell Membrane / Q000648:ultrastructure; D003902:Detergents; D006801:Humans; D007158:Immunologic Techniques; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000502:physiology* / Q000648:ultrastructure*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000648:ultrastructure*; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003902:Detergents; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell