A DIFFERENTIAL-AVIDITY MODEL FOR T-CELL SELECTION

The processes of positive and negative selection during thymic development shape the repertoires of antigen specificities displayed by T cells. This rids the animal of potentially autoreactive T cells and, at the same time, ensures that they are capable of major histocompatibility complex (MHC)-restricted recognition of antigen. Paradoxically, both processes involve the engagement of the T-cell receptor (TCR) on immature thymocytes with peptide/MHC complexes expressed on thymic stromal cells. Here, Philip Ashton-Rickardt and Susumu Tonegawa suggest that the critical parameter determining the outcome of this interaction is the number of TCRs occupied by peptide/MHC complexes and that this, in turn, is determined by the avidity of the TCR-MHC interaction: low avidity resulting in positive selection and high avidity resulting in negative selection.