Differential APC requirements of self- and nonself-reactive T cells and T cell hybridomas specific for retinal...

Autoreactive T cell hybridomas specific for pathogenic peptides of retinal S-Ag require a novel radiosensitive APC activity for IL-2 secretion that is distinct from Ag presentation by MHC class II. Antigen-dependent IL-2 secretion by self-reactive hybridomas was much more efficient with splenic APC than with thymic APC, although both provided similar levels of hybridoma TCR occupancy as measured by activation-induced cell death. Furthermore, thymic APC did stimulate IL-2 secretion by a non-self reactive hybridoma. To test the hypothesis that this activity was provided by a distinct cell population, fractionated splenocytes were tested for their ability to present Ag to these hybridomas. The most potent Ag presentation for IL-2 secretion was found to segregate with low-density, B cell-enriched fractions while adherent cells, or purified T cells were unable to support IL-2 production. Together with previous results, the data show that antigen presentation leading to IL-2 secretion by these autoreactive T cell hybridomas requires activated B cells, whereas TCR occupancy can be provided by several APC subsets.