Positive and negative selection of a iymphocytic choriomeningitis ViNS (LCMV) peptide-Specifk, K2Dbrestricted T cell clone (P14) was studied using TAP1-and TAP1+ mice transgenic for P14 T cell receptor (TCR) a and 8 genes. Positive selection of transgenic CD8+ Pi 4 ceils was impaired in TAP1-mice. Addition of the LCMV peptlde to TAPl-fetal thymic organ cuitures (PTOCs) at low and high concentrations induced positive and negative selection of CD8+ P14 cells, respectiveiy, white addition of the same peptide to TAP1+ FTOCs induced negative selection even at tow concentmtions. Both types of selection were peptide specific. Thus, a critical parameter that controls the fate of a thymocyte seems to be the number of TCRs engaged with complexes of peptide and major histocompatibility complex. When this number is low, positive seiection occurs, and when it is high, negative selection takes place. These findings support a differential avidity model of T ceil selection. introduction

The repertoire of antigen specificities of T cells of an individual animal is shaped by two types of cellular selection that take place in the thymus. Positive selection (Bevan, 1977; Zinkernagel et al., 1978) ensures that T cells leaving the thymus are capable of major histocompatibility complex (MHC)-restricted recognition of antigen; that is, they possess the capacity to recognize antigen presented by products of self-MHC (Zinkernagel and Doherty, 1974; Fink and Bevan, 1978). Positive selection is thought to involve engagement of T cell receptors (TCRs) on immature CD3+ low CD4+ CD8+ thymocytes with self-MHC products expressed on the surface of thymic epithelial cells (Lo and Sprent, 1988): only those thymocytes expressing