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.
Ludger Klein  1 ,  Bruno Kyewski  2 ,  Paul M Allen  3 ,  Kristin A Hogquist  4
Affiliations
  • 1. Institute for Immunology, Ludwig Maximilians University, 80336 Munich, Germany.
  • 2. Division of Developmental Immunology, German Cancer Research Center, 69120 Heidelberg, Germany.
  • 3. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
  • 4. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55414, USA.
PMID: 24830344 DOI: 10.1038/nri3667
Abstract

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.