Identification of immunodominant donor MHC peptides following rejection and donor strain transfusion-induced tolerance of heart allografts in adult rats

Pre-graft priming of heart allograft recipients with donor strain blood ind uces tolerance in 100% of adult rats in the congenic LEW.1W to LEW.1A combi nation. This tolerant state is specific for donor MHC antigens as third-par ty blood transfusions fail to induce tolerance, and third-party skin grafts are promptly rejected by tolerant graft recipients. In this study we have characterized the immunodominant donor (RT1(U)) class I and II allogenic pe ptides which elicit an in vitro proliferative response to splenocytes from recipients (RT1(a)) undergoing acute rejection or tolerant to a LEW.1A card iac allograft. Paradoxically, splenocytes from tolerant animals responded m ore vigorously to a broader set of donor peptides than splenocytes from rej ecting animals. In addition, several of these peptides were observed to be stimulatory only for tolerant splenocytes. These findings suggest that regu latory cells may be involved in tolerance induction or maintenance and are selected by specific motifs, which could be utilized for manipulating the i mmune system of graft recipients.