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

Ludger Klein, Bruno Kyewski, Paul M. Allen, Kristin A. Hogquist

Research output: Contribution to journalReview articlepeer-review

943 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)377-391
Number of pages15
JournalNature Reviews Immunology
Issue number6
StatePublished - Jun 2014

Bibliographical note

Funding Information:
L.K. received support from the Deutsche Forschungsgemeinschaft, Germany (Collaborative research centre SFB 1054 and grants KL 1228/4‑1 and KL 1228/5‑1). B.K. was supported by the German Cancer Research Center (DKFZ), the Deutsche Forschungsgemeinschaft (Collaborative research centre SFB 938) and the European Research Council (ERC‑2012‑AdG). P.M.A. was supported by the US National Institutes of Health (NIH) grant AI‑24157.K.A.H is supported by NIH grants AI088209, AI35296 and AI39560.


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