Positive and negative selection of T cells

Annu Rev Immunol. 2003;21:139-76. doi: 10.1146/annurev.immunol.21.120601.141107. Epub 2002 Oct 16.


A functional immune system requires the selection of T lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens. This selection occurs predominantly in the thymus, where lymphocyte precursors first assemble a surface receptor. In this review we summarize the current state of the field regarding the natural ligands and molecular factors required for positive and negative selection and discuss a model for how these disparate outcomes can be signaled via the same receptor. We also discuss emerging data on the selection of regulatory T cells. Such cells require a high-affinity interaction with self-antigens, yet differentiate into regulatory cells instead of being eliminated.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Clonal Deletion
  • Epithelial Cells / immunology
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Humans
  • Mice
  • Models, Immunological
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcription Factors / metabolism


  • Receptors, Antigen, T-Cell
  • Transcription Factors