Kinetic proofreading in T-cell receptor signal transduction.

作者：Timothy W. McKeithan · 发表于：Proceedings of the National Academy of Sciences · 年份：1995 · DOI：10.1073/pnas.92.11.5042 · 被引用次数：1011 · 研究领域：Monoclonal and Polyclonal Antibodies Research、T-cell and B-cell Immunology、CAR-T cell therapy research

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.