Ligand thresholds at different stages of T cell development.

Certain T cell ligands can stimulate most or all T cells whose receptor is encoded by particular V beta genes. Exposure to these same ligands during intrathymic development leads to deletion of T cells bearing these same receptors. We have utilized one such ligand, staphylococcal enterotoxin B (SEB), to examine the quantitative differences in these two responses. By comparing the dose of SEB required to delete developing T cells in thymic organ culture with that required to stimulate spleen cells to expand clonally, we observe that clonal deletion is one to two orders of magnitude more sensitive to SEB. Because the T cell ligand involves not only SEB but also class II MHC molecules, and because the culture conditions are distinct, this system does not allow one to state that intrathymic T cells are intrinsically more sensitive to negative selection than peripheral T cells are to activation. However, these studies for the first time do establish a quantitative comparison of these two processes and suggest that there is a margin for error built into the clonal deletion process, such that ligands presented in the thymus are 30- to 100-fold more active in clonal deletion than is the same ligand in activation of peripheral T cells. This result agrees well with the observation that naturally occurring unknown ligands associated with I-E can clonally delete cells that are not activated by the same ligand in mixed lymphocyte culture.