Indirect T cell allorecognition of donor antigens contributes to the rejection of vascularized kidney allografts.

Abstract

This report demonstrates for the first time that indirect T cell allorecognition of donor antigens can contribute to the effector mechanism of rejection of vascularized organ allografts. LEW (RT1(1)) rats were primed for indirect T cell allorecognition of DA (RT1av1) classical class I MHC molecules by immunization with synthetic 22-24 amino acid peptides corresponding to the alpha-helices of the RT1-A class I molecule. These rats received (DA x LEW) F1 kidney grafts that had been depleted of donor interstitial dendritic cells to minimize the direct T cell allorecognition response to the graft. The peptide-immunized rats rejected their grafts more rapidly than did control immunized rats, in terms of both graft function and survival. Moreover, the kinetics of antibody production to intact donor class I molecules after kidney transplantation was much more rapid in the peptide-immunized rats, suggesting that T cell help is the rate-limiting factor for antibody production to donor antigens in this model. It was of interest that we could not detect an antibody response to donor peptides after kidney graft rejection.