Presentation of antigen, foreign major histocompatibility complex proteins and self by thymus cortical epithelium

In mouse and man most peripheral T cells bear clonally variable receptors made up of alpha- and beta-chains which bind ligands on target cells consisting of peptide fragments of foreign antigens, complexed with cell surface proteins encoded by the major histocompatibility complex (MHC) of the individual. In the thymus, developing T cells are selected to mature only if their receptors will be able to participate in self-MHC plus antigen recognition in the periphery. This positive selection occurs in the presence of self-MHC, but in the apparent absence of antigen, leading to the paradoxical conclusion that developing thymocytes must be positively selected by engagement of their receptors and self-MHC alone, although thymocytes that react too well with self-MHC are eliminated. To account for this, it has been suggested that MHC molecules in the thymus are not identical to those found elsewhere. To test this and other hypotheses, we have examined the ability of the presumed selecting cells, those of the thymus cortical epithelium, to present various MHC complexes to T cells. Our results indicate that MHC molecules on thymus epithelium are not always the same as those found elsewhere.