T-CELL RECEPTOR ANTAGONIST PEPTIDES INDUCE POSITIVE SELECTION

We have used organ culture of fetal thymic lobes from T cell receptor (TCR) transgenic beta2M(-/-) mice to study the role of peptides in pos itive selection. The TCR used was from a CD8+ T cell specific for oval bumin 257-264 in the context of K(b). Several peptides with the abilit y to induce positive selection were identified. These peptide-selected thymocytes have the same phenotype as mature CD8+ T cells and can res pond to antigen. Those peptides with the ability to induce positive se lection were all variants of the antigenic peptide and were identified as TCR antagonist peptides for this receptor. One peptide tested, E1, induced positive selection on the beta2M(-/-) background but negative selection on the beta2M(+/-) background. These results show that the process of positive selection is exquisitely peptide specific and sens itive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.