This grant proposal seeks to better understand the positive and negative selective forces which shape the T cell repertoire and the general focus of the grant is on the characterization of non-MHC genes which influence thymic selection. We plan to continue characterizing a gene, Et-1, that is absolutely required for the clonal deletion of I-E reactive cells and whose corresponding gene product is likely a member of the M1s-family of antigens. The molecular relationship between Et-1 and the endogenous viral genome, Mtv-9, will be determined. A second I-E co-tolerogen, Et- 2, present in the DBA/2 strain will be characterized with an emphasis on determining whether or not it is related to endogenous viral sequences. To study the effects of non-MHC genes on positive selection, we will carry out an analysis of the background (non-MHC) genes which determine the frequency of V-beta-11+/CD8+T cells. Finally, we will study the effects of background genes on the positive selection of a single T cell receptor in a T cell receptor transgenic mouse.