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PMID: 1828760 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Pairwise, cooperative and inhibitory interactions describe the assembly and probable structure of the T-cell antigen receptor.

The EMBO journal ·Vol. 10 ·No. 7 ·1991-07-00 ·Pages 1643-51

Manolios N, Letourneur F, Bonifacino JS, Klausner RD

Abstract

The T-cell antigen receptor (TCR) is a multi-subunit complex consisting of clonotypic heterodimers (TCR-alpha beta or TCR-gamma delta) that are non-covalently linked to at least four invariant chains (CD3-delta, -epsilon, -gamma; and zeta or eta). The ordered process of assembly and the final number of individual chains that comprise the TCR is unclear. In this study, we examined the molecular basis of subunit interactions and the component requirements leading to the formation of a complete TCR. Analysis of transient cotransfections in monkey kidney fibroblasts (COS cells) showed assembly between selective chain pairs. Multiple chain cotransfections demonstrated the formation of stable higher order partial complexes. Assembly of such subcomplexes was facilitated by cooperative interactions between clonotypic and invariant CD3 chains. When zeta was cotransfected with any TCR component, no pairwise interaction was detected. Only when there was coexpression of all of the other TCR chains (TCR-alpha, -beta, CD3- epsilon, -gamma, -delta) did zeta assemble with the TCR complex. Not all chain pairs formed stable heterodimers. For one such pair, lack of assembly is due to the inhibitory effects of negatively charged residues within their transmembrane domains. The combined effects of these interactions probably determine the assembly and the quaternary structure of the TCR complex.

MeSH Terms
Animals Antibodies/immunology Antigen-Antibody Reactions Antigens, CD/immunology Antigens, Differentiation, T-Lymphocyte/immunology CD3 Complex Cell Line Chlorocebus aethiops Clone Cells/immunology DNA/biosynthesis Protein Conformation Receptors, Antigen, T-Cell/chemistry,immunology Structure-Activity Relationship Transfection
Chemicals
Antibodies Antigens, CD Antigens, Differentiation, T-Lymphocyte CD3 Complex Receptors, Antigen, T-Cell DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Manolios N
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Letourneur F
Bonifacino J S
Klausner R D
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-07-00
Pages
1643-51
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452834
Subset
IM
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