The Immunology of Allograft Rejection: A Survey of Current Knowledge and a Discussion of Peptide-Specific Anti-Rejection Strategies

The goal of transplantation immunology is to develop strategies for antigen-specific inhibition of transplant rejection. The immune response triggered in the host by the MHC-incompatible organ transplant can lead to the loss of organ function. The MHC peptides created by antigen processing of the donor- or allo-MHC molecules of the transplant are a major stimulus for activation of alloreactive CD4+ T cells in the recipient. The T cells activated via this pathway of indirect alloantigen recognition are among the determining factors in the pathogenesis of both acute and chronic rejection. Since activated CD4+ T cells control by means of their cytokines both the cellular and humoral arms of the adaptive immune response, they are a key element in the search for effective immunomodulating therapeutic strategies. According to current knowledge, regulatory T cells play a crucial role in the immune response. Even though antigen-independent factors, such as ischemia and reperfusion injury, also participate in the multi-factorial process of rejection, the allogeneic immune response depends mainly on the MHC incompatibility between donor and host. It remains for future studies to determine the extent to which antigen-specific modulation of the allogeneic T cells is able to effectively control this multicellular process.