Self-antigen presentation by thymic stromal cells: a subtle division of labor

Self-antigen–MHC complexes expressed by thymic stromal cells serve as ligands for TCR-mediated positive and negative selection, resulting in a self-MHC-restricted, self-tolerant T cell repertoire. It has recently become apparent that thymic stromal cells differ in their accessibility to antigen as well as their ability to process and present antigen. These differences result in the sampling by thymic stromal cells of largely nonoverlapping self-antigen pools and the display of self-peptide profiles specific for each cell type. In conjunction with single or serial cell–cell interactions between thymocytes and stromal cells, such differences in self-antigen display allow for maximal (re)presentation of ‘self’ in the thymus and optimize the efficacy of positive and negative selection.