Positive Selection of T Cells Induced by Viral Delivery of Neopeptides to the Thymus

Abstract

The relation between an antigenic peptide that can stimulate a mature T cell and the natural peptide that promoted selection of this cell in the thymus is still unknown. An experimental system was devised to address this issue in vivo—mice expressing neopeptides in thymic stromal cells after adenovirus-mediated delivery of invariant chain-peptide fusion proteins. In this system, selection of T cells capable of responding to a given antigenic peptide could be promoted by the peptide itself, by closely related analogs lacking agonist and antagonist activity, or by ostensibly unrelated peptides. However, the precise repertoire of T cells selected was dictated by the particular neopeptide expressed.