Kinetic proofreading in T-cell receptor signal transduction.
Like other cell-surface receptors with intrinsic or associated protein-tyrosine kinase activity, the T-cell receptor complex undergoes a number of modifications, including tyrosine phosphorylation steps, after ligand binding but before transmitting a signal. The requirement for these modifications introduces a temporal lag between ligand binding and receptor signaling. A model for the T-cell receptor is proposed in which this feature greatly enhances the receptor's ability to discriminate between a foreign antigen and self-antigens with only moderately lower affinity. The proposed scheme is a form of kinetic proofreading, known to be essential for the fidelity of protein and DNA synthesis. A variant of this scheme is also described in which a requirement for formation of large aggregates may lead to a further enhancement of the specificity of T-cell activation. Through these mechanisms, ligands of different affinity potentially may elicit qualitatively different signals.
McKeithan
T W
TW
Department of Pathology, University of Chicago, IL 60637, USA.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D004247:DNA / Q000096:biosynthesis; D007700:Kinetics; D008285:Major Histocompatibility Complex; D018448:Models, Immunological; D008962:Models, Theoretical; D014176:Protein Biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D004247:DNA; D020794:Receptor Protein-Tyrosine Kinases