title: Codification of bidentate pMHC interaction with TCR and its co-receptor.
abstract: A 1983 Immunology Today rostrum hypothesized that each T cell has two recognition units: a T cell receptor (TCR) complex, which binds antigen associated with a polymorphic region of a MHC molecule (pMHC), and a CD4 or CD8 molecule that binds to a conserved region of that same MHC gene product (class II or I, respectively). Structural biology has since precisely revealed those bidentate pMHC interactions. TCRαβ ligates the membrane-distal antigen-binding MHC platform, whereas CD8 clamps a membrane-proximal MHCI α3 domain loop and CD4 docks to a hydrophobic crevice between MHCII α2 and β2 domains. Here, we review how MHC class-restricted binding impacts signaling and lineage commitment, discussing TCR force-driven conformational transitions that may optimally expose the co-receptor docking site on MHC.
authors.affiliation: Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ellis_reinherz@dfci.harvard.edu.
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
authors.affiliation: Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jia-huai
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell
keywords: TCR; antigen recognition; co-receptor; mechanobiology
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