Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see).
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.
Institute for Immunology, Ludwig Maximilians University, 80336 Munich, Germany.
Ludger
L
Klein
Division of Developmental Immunology, German Cancer Research Center, 69120 Heidelberg, Germany.
Bruno
B
Kyewski
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Paul M
PM
Allen
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55414, USA.
Kristin A
KA
Hogquist
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D060833:Cellular Microenvironment / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D038041:Lymphopoiesis / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D060168:Thymocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell