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

Here, the authors describe the key characteristics of the different antigen-presenting cell (APC) populations that govern T cell development in the thymus. They discuss how the interactions that occur between thymocytes and thymic APCs shape the mature T cell repertoire, and how they subsequently affect the nature of peripheral immune responses. 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.