Affinity threshold for thymic selection through a T-cell receptor-co-receptor zipper

Nat Rev Immunol. 2009 Mar;9(3):207-13. doi: 10.1038/nri2469.


The affinity of the T-cell receptor (TCR) for self antigen is the basis for the selection of a useful (MHC-restricted) and safe (self-tolerant) T-cell repertoire. However, it has been difficult to understand how thymocytes measure ligand affinity and translate this signal into a cellular response. In this Opinion article, we propose a new model that describes how the TCR discriminates between low- and high-affinity ligands, which is based on the duration of TCR-ligand interactions and a 'zipper' mechanism that mediates the interaction of the TCR and co-receptor molecules to initiate negative-selection signalling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • Humans
  • Lymphopoiesis
  • Major Histocompatibility Complex / physiology
  • Mice
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / immunology*


  • Autoantigens
  • Receptors, Antigen, T-Cell