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Subunit interactions within the T-cell antigen receptor: clues from the study of partial complexes
J S Bonifacino1, C Chen, J Lippincott-Schwartz
1Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
Abstract:
The T-cell antigen receptor is a multisubunit complex composed of seven transmembrane chains (alpha beta gamma delta epsilon zeta 2). Subunit interactions within this complex were defined by analyzing the subunit composition of partial complexes. These partial complexes were observed in mutant and tumor T cells that fail to synthesize one or more of the receptor chains or in fibroblasts transfected with genes encoding T-cell antigen receptor chains. In addition, partial complexes were generated by immunoprecipitation with antibodies that cause selective dissociation of T-cell antigen receptor chains. The alpha and beta chains were found to form a disulfide-linked dimer in the absence of any of the other chains. The gamma, delta, and epsilon chains were also efficiently associated in the absence of a complete heterodimer. Complexes composed only of delta epsilon or gamma epsilon could be observed. Both these dimers, as well as the gamma delta epsilon trimer, could form stable complexes with alpha beta, even in the absence of zeta 2. The zeta 2 dimer could bind directly to alpha beta. In the absence of a complete clonotypic heterodimer, zeta 2 was not stably associated with gamma delta epsilon. These observations suggest a model in which alpha beta interacts directly with the gamma delta epsilon trimer and zeta 2, with less-direct interaction between the latter two.
Insights
The T-cell antigen receptor (TCR) complex involves multiple protein chains. This study elucidates how different TCR subunits, like alpha beta and gamma delta epsilon, interact to form functional complexes, crucial for T-cell immunity.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The T-cell antigen receptor (TCR) is a critical molecular complex on T lymphocytes.
- Understanding TCR subunit assembly is key to T-cell function and immune response.
Purpose of the Study:
- To define the specific interactions between subunits of the T-cell antigen receptor complex.
- To elucidate the assembly pathway of the TCR.
Main Methods:
- Analysis of partial TCR complexes from mutant T cells and transfected fibroblasts.
- Immunoprecipitation using antibodies to induce selective chain dissociation.
Main Results:
- Alpha (α) and beta (β) chains form a disulfide-linked dimer independently.
- Gamma (γ), delta (δ), and epsilon (ε) chains associate efficiently, forming dimers (δ-ε, γ-ε) and a trimer (γ-δ-ε).
- The αβ dimer stably associates with the γδε trimer and the zeta (ζ) 2 dimer, with ζ2 binding directly to αβ.
Conclusions:
- A model is proposed where αβ directly interacts with the γδε trimer and ζ2.
- Interactions within the TCR complex are hierarchical, allowing assembly even with missing subunits.
- This provides insights into TCR assembly and stability.