Positive and negative selection, self-nonself discrimination and the roles of costimulation and anergy

It is still unclear whether the adaptive immune system can perform accurate self-nonself discrimination and what could influence its performance. Starting from simple cellular interaction rules we show that it is possible to achieve perfect self-nonself discrimination in a consistent framework provided positive and negative selection operate during repertoire education, and costimulation and anergy are also considered during T cell activation. In this theory T cell receptors diversity is required for cells to sense differently different peptides; positive selection is needed to guarantee maximal lymphocyte's interactivity and to allow negative selection to reduce conjugation lifetimes maximally; costimulation is necessary to signal that an antigen presenting cell established an uncommon rate of long lived conjugations when presenting foreign peptides; anergy is required to guarantee that these stable contacts involved different T cells and not always the same. These results suggest that accurate self-nonself discrimination can have shaped the adaptive immune system.