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. 1995 May 23;92(11):5042–5046. doi: 10.1073/pnas.92.11.5042

Kinetic proofreading in T-cell receptor signal transduction.

T W McKeithan 1
PMCID: PMC41844  PMID: 7761445

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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Selected References

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