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The structural basis of αβ T‐lineage immune recognition: TCR docking topologies, mechanotransduction, and co‐receptor function
Author(s) -
Wang Jiahuai,
Reinherz Ellis L.
Publication year - 2012
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2012.01161.x
Subject(s) - t cell receptor , immunological synapse , biology , major histocompatibility complex , ectodomain , microbiology and biotechnology , t cell , acquired immune system , immune system , antigen , immunology , receptor , genetics
Summary Self versus non‐self discrimination is at the core of T ‐lymphocyte recognition. To this end, αβ T ‐cell receptors ( TCR s) ligate ‘foreign’ peptides bound to major histocompatibility complex ( MHC ) class I or class II molecules (p MHC ) arrayed on the surface of antigen‐presenting cells ( APC s). Since the discovery of TCR s approximately 30 years ago, considerable structural and functional data have detailed the molecular basis of their extraordinary ligand specificity and sensitivity in mediating adaptive T ‐cell immunity. This review focuses on the structural biology of the Fab‐like TCR αβ clonotypic heterodimer and its unique features in conjunction with those of the associated CD 3εγ and CD 3εδ heterodimeric molecules, which, along with CD 3ζζ homodimer, comprise the TCR complex in a stoichiometry of 1:1:1:1. The basis of optimized TCR αβ docking geometry on the p MHC linked to TCR mechanotransduction and required for T ‐cell signaling as well as CD 4 and CD 8 co‐receptor function is detailed. A model of the TCR ectodomain complex including its connecting peptides suggests how force generated during T ‐cell immune surveillance and at the immunological synapse results in dynamic TCR quaternary change involving its heterodimeric components. Potential insights from the structural biology relevant to immunity and immunosuppression are revealed.