The processes of positive and negative selection during thymic development shape the repertoires of antigen specificittes displayed by T cells. This rids the animal of potentialS, autoreactive T cells and, at the same time, em, ures that they are capable of maior histocompatibilit3, complex (MHC)-restricted recognition of antigen. Paradoxically both processes invoh, e the engagement of the% cell receptor (TCR) on immature tbymocytes wub peptide/MHC complexes expressed on thymic stromal cells. Here, Philip Ashton-Rickardt and Sttsttmlt Tonegawa suggest that the critical parameter determining the outcome of this interaction is the number of TCRs occupied b3 peptide/MHC complexes and that this, in turn, is determined by the avidita'o [the TCR-MHC interaction: low avidity resulting in positive selection and high avidt O, resulting in negative selection.

The molecular recognition of antigen is fundamental to the adaptive immune system in aUowing the host animal not only to respond to potentially pathogenic invaders, but also to distinguish these invaders from benign self components. Unlike the antigen receptor of B cells, which can bind free antigen, T-cell receptors (TCRs) recognize complexes composed of antigen-derived peptides and self major histocompatibility complex (MHC) molecules. Thus, the TCR exhibits dual specificities, one for the antigen and the other for the MHC molecule, the