Paradoxical intrathymic positive selection in mice with only a covalently presented agonist peptide

The Y-Ae mAb and the 1H3.1 alpha beta T cell antigen receptor (TCR) are bot h specific for the I-E alpha 52-68 peptide bound to the I-A(b) major histoc ompatibility complex (MHC) class II molecule. Antigen-presenting cells (APC s) from I-A(b+) mice with a natural or transgenic (Tg) I-Ea chain activate mature 1 H3.1 T cells and cause the deletion of 1 H3.1 TCR Tg thymocytes. H owever, 1 H3.1 T cells were neither activated nor inactivated by confrontat ion with APCs from I-Ab-Ep mice in which I-A(b) molecules are occupied only by the covalently associated E alpha 52-68 peptide. Instead, immature 1H3. 1 TCR Tg thymocytes were efficiently positively selected into the CD4 linea ge in the I-Ab-Ep thymus. This selection relied on specific recognition of the E alpha 52-68/I-A(b) complex because it was blocked by Y-Ae. 1H3.1 TCR Tg T cells maturing in the I-Ab-Ep thymus efficiently populated the periphe ry, displayed a naive phenotype, and were specifically reactive to the Ea52 -68 peptide or to I-A(b)+I-E alpha (+) APCs, indicating that 1 H3.1 T cells were not antagonized in I-Ab-Ep mice. The data identify major histocompati bility complex class II molecules with only a covalently attached self-pept ide as a ligand for in vivo positive selection of T cells specific for the same peptide.