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Revisiting the putative TCR C? dimerization model through structural analysis.

ABSTRACT: Despite major advances in T cell receptor (TCR) biology and structure, how peptide-MHC complex (pMHC) ligands trigger ?? TCR activation remains unresolved. Two views exist. One model postulates that monomeric TCR-pMHC ligation events are sufficient while a second proposes that TCR-TCR dimerization in cis via C? domain interaction plus pMHC binding is critical. We scrutinized 22 known TCR/pMHC complex crystal structures, and did not find any predicted molecular C?-C? contacts in these crystals that would allow for physiological TCR dimerization. Moreover, the presence of conserved glycan adducts on the outer face of the C? domain preclude the hypothesized TCR dimerization through the C? domain. Observed functional consequences of C? mutations are likely indirect, with TCR microclusters at the immunological synapse driven by TCR transmembrane/cytoplasmic interactions via signaling molecules, scaffold proteins, and/or cytoskeletal elements.

SUBMITTER: Wang JH

PROVIDER: S-EPMC3558723 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Revisiting the putative TCR Cα dimerization model through structural analysis.

Wang Jia-Huai JH Reinherz Ellis L EL

Frontiers in immunology 20130130

Despite major advances in T cell receptor (TCR) biology and structure, how peptide-MHC complex (pMHC) ligands trigger αβ TCR activation remains unresolved. Two views exist. One model postulates that monomeric TCR-pMHC ligation events are sufficient while a second proposes that TCR-TCR dimerization in cis via Cα domain interaction plus pMHC binding is critical. We scrutinized 22 known TCR/pMHC complex crystal structures, and did not find any predicted molecular Cα-Cα contacts in these crystals th ...[more]

PMID: 23386853

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