Influence of the affinity of selecting ligands on T cell positive and negative selection and the functional maturity of the positively selected T cells.

Interaction of the TCR on immature thymocytes with ligands on antigen presenting cells can lead to different fates including positive and negative selection. The affinity of the selecting ligands plays an important role in determining these outcomes. We used the 2C TCR transgenic model to evaluate the efficacy of ligands with widely differing affinity (3 x 10(3) - 2 x 10(6) M-1) for the 2C TCR in mediating thymic negative and positive selection. Our results support the conclusions that the deletion of immature thymocytes is not only mediated by high-affinity ligands but also by low-affinity/avidity ligands. However, high- and low-affinity ligands differ in their requirements for negative selection. We also present evidence that positive selection is not an all or none process but depending on the strength of interaction between the ligand and the TCR during the positive selection process can result in single positive thymocytes that are at different stages of functional maturity.