POSITIVE AND NEGATIVE THYMOCYTE SELECTION INDUCED BY DIFFERENT CONCENTRATIONS OF A SINGLE PEPTIDE

T lymphocyte maturation is dependent on interactions between the T cel l receptor (TCR) expressed on the developing thymocyte and intrathymic major histocompatibility complex (MHC)-peptide ligands. The relation between the peptide-MHC complex that results in negative or positive s election has not been identified. Here, the requirements for the matur ation of thymocytes expressing a defined transgenic TCR specific for a viral peptide are studied in fetal thymic organ culture. Low concentr ations of the viral peptide antigen recognized by this transgenic TCR can mediate positive selection, whereas high concentrations result in thymocyte tolerance. These findings support the affinity-avidity model of thymocyte selection.