INHIBITION OF INTRATHYMIC T-CELL DEVELOPMENT BY EXPRESSION OF A TRANSGENIC ANTAGONIST PEPTIDE

The mature T cell receptor (TCR) repertoire is shaped by positive- and negative-selection events taking place during T cell development. The se events are regulated by interactions between the TCR and major hist ocompatibility complex molecules presenting self-peptides. It has been shown that many antagonist peptides are efficient at mediating positi ve selection. In this study we analyzed the effects of a transgene enc oding an antagonist peptide (influenza NP34) that is presented by H-2D (b) in a Tap-1-independent fashion in mice expressing the influenza NP 68-specific TCR F5. We find that the transgenic peptide does not media te positive or negative selection in F5(+)Tap-1(-/-) mice, but inhibit s maturation of CD8(+) single positive thymocytes in F5(+)Tap-1(+) mic e without inducing signs of negative selection. We conclude that antag onism of antigen recognition occurs not only at the level of mature T cells but also in T cell development.