A DIFFERENTIAL-AVIDITY MODEL FOR T-CELL SELECTION

The processes of positive and negative selection during thymic develop ment shape the repertoires of antigen specificities displayed by T cel ls. This rids the animal of potentially autoreactive T cells and, at t he same time, ensures that they are capable of major histocompatibilit y complex (MHC)-restricted recognition of antigen. Paradoxically, both processes involve the engagement of the T-cell receptor (TCR) on imma ture 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 av idity resulting in positive selection and high avidity resulting in ne gative selection.