T cell receptor antagonist peptides induce positive selection

We have used organ culture of fetal thymic lobes from T cell receptor (TCR) transgenic β2M(−/−) mice to study the role of peptides in positive selection. The TCR used was from a CD8+ T cell specific for ovalbumin 257–264 in the context of Kb. Several peptides with the ability to induce positive selection were identified. These peptide-selected thymocytes have the same phenotype as mature CD8+ T cells and can respond to antigen. Those peptides with the ability to induce positive selection 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 β2M(−/−) background but negative selection on the β2M(+/−) background. These results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.