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Title:
Kinetic Proofreading in T-Cell Receptor Signal Transduction
Authors:
McKeithan, Timothy W.
Publication:
Proceedings of the National Academy of Sciences of the United States of America, Volume 92, Issue 11, pp. 5042-5046
Publication Date:
05/1995
Origin:
JSTOR
Bibliographic Code:
1995PNAS...92.5042M

Abstract

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.

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