An induced rebinding model of antigen discrimination.
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.
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