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An induced rebinding model of antigen discrimination.
Dushek, Omer; van der Merwe, P Anton.
Affiliation
  • Dushek O; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK; Wolfson Centre for Mathematical Biology, University of Oxford, Oxford, UK. Electronic address: omer.dushek@path.ox.ac.uk.
  • van der Merwe PA; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. Electronic address: anton.vandermerwe@path.ox.ac.uk.
Trends Immunol ; 35(4): 153-8, 2014 Apr.
Article in En | MEDLINE | ID: mdl-24636916
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphocyte Activation / Receptors, Antigen, T-Cell / Models, Immunological / Major Histocompatibility Complex Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Trends Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2014 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Lymphocyte Activation / Receptors, Antigen, T-Cell / Models, Immunological / Major Histocompatibility Complex Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Trends Immunol Journal subject: ALERGIA E IMUNOLOGIA Year: 2014 Type: Article