Intrathymic presentation of circulating non-major histocompatibility complex antigens.

Intrathymic selection of T-cell specificity has been shown to be influenced by self-major histocompatibility complex (MHC) antigens encoded by radioresistant thymic stromal cells. The role of non-MHC antigens in intrathymic T-cell differentiation, in particular induction of antigen-specific tolerance, has been unclear and the access of non-MHC antigens to the thymus is controversial. Here we present evidence that circulating protein antigens enter the thymus and are presented by thymic stromal cells. At least three distinct types of stromal cells are thought to be associated with intrathymic lymphopoiesis; after intravenous (i.v.) injection of antigen only I-A/E-positive medullary dendritic cells, but not I-A/E-negative macrophages or I-A/E-positive cortical epithelial cells co-purified with antigen-specific stimulation of cloned T-helper cells in vitro. Antigen presentation by thymic stromal cells was dependent on the dose of antigen injected and the time interval after injection.