Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see)

Nat Rev Immunol. 2014 Jun;14(6):377-91. doi: 10.1038/nri3667. Epub 2014 May 16.


The fate of developing T cells is specified by the interaction of their antigen receptors with self-peptide-MHC complexes that are displayed by thymic antigen-presenting cells (APCs). Various subsets of thymic APCs are strategically positioned in particular thymic microenvironments and they coordinate the selection of a functional and self-tolerant T cell repertoire. In this Review, we discuss the different strategies that these APCs use to sample and process self antigens and to thereby generate partly unique, 'idiosyncratic' peptide-MHC ligandomes. We discuss how the particular composition of the peptide-MHC ligandomes that are presented by specific APC subsets not only shapes the T cell repertoire in the thymus but may also indelibly imprint the behaviour of mature T cells in the periphery.

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology
  • Cellular Microenvironment / immunology
  • Dendritic Cells / immunology*
  • Humans
  • Immune Tolerance*
  • Lymphopoiesis / immunology
  • Mice
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Thymocytes / immunology*
  • Thymus Gland / immunology


  • Autoantigens
  • Receptors, Antigen, T-Cell