The in vivo fate of APCs displaying minor H antigen and/or MHC differencesis regulated by CTLs specific for immunodominant class I-associated epitopes

The goal of this work was to evaluate the fate of APCs following interactio ns with T cells in unprimed mice with a normal T cell repertoire. We elabor ated a model in which male adherent peritoneal mononuclear cells were injec ted into the foreleg footpads of naive female recipients mismatched for eit her minor or major histocompatibility Ags, At various times after injection , APC numbers in the draining (axillary and brachial) lymph nodes were asse ssed using a Ubely gene-specific PCR assay. Our experimental model was desi gned so that the number of APCs expressing the priming epitope was similar to what is observed under real life conditions. Thus, early after injection , the frequency of afferent lymph-derived APCs expressing the printing epit ope was in the range of 10(1)-10(2)/10(6) lymph node cells. We found that A PCs presenting some, but not all, nonself epitopes were killed rapidly afte r entrance into the lymph nodes. Rapid elimination of APCs occurred followi ng interactions with MWC class I-restricted, but not class II-restricted, T cells and was observed when APCs presented an immunodominant (B6(dom1)/N7( a)). but not a nondominant (HY), epitope, Killing of APCs was mediated part ly, but not exclusively, by perforin-dependent process. We propose that kil ling of APCs by CTLs specific for immunodominant MHC class I-restricted epi topes may be instrumental in regulating the intensity, duration, and divers ity of T cell responses.