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T cells have to detect rare high-affinity 'foreign' peptide MHC (pMHC) ligands among abundant low-affinity 'self'-peptide MHC ligands. It remains unclear how this remarkable discrimination is achieved. Kinetic proofreading mechanisms can provide the required specificity but only at the expense of much reduced sensitivity. A number of recent observations suggest that pMHC engagement of T cell receptors (TCRs) induces changes such as clustering and/or conformational alterations that enhance subsequent rebinding. We show that inclusion of induced rebinding to the same pMHC in kinetic proofreading models enhances the sensitivity of TCR recognition while retaining specificity. Moreover, induced rebinding is able to reproduce the striking, and hitherto unexplained, 2D membrane-binding properties recently reported for the TCR.

Original publication

DOI

10.1016/j.it.2014.02.002

Type

Journal article

Journal

Trends Immunol

Publication Date

04/2014

Volume

35

Pages

153 - 158

Keywords

Animals, Humans, Lymphocyte Activation, Major Histocompatibility Complex, Models, Immunological, Protein Binding, Receptors, Antigen, T-Cell, Self Tolerance