Pathways of Antigen Recognition by T Cells in Allograft Rejection

The adaptive immune response leading to the rejection of allogeneic transplants is initiated and orchestrated by recipient T cells recognizing donor antigens. T-cell allorecognition is mediated via 3 distinct mechanisms: the direct pathway in which T cells recognize allogeneic major histocompatibility complex (MHC) molecules on donor cells, the indirect pathway through which T cells interact with donor peptides bound with self-MHC molecules on recipient antigen-presenting cells, and the recently described semidirect pathway whereby T cells recognize donor MHC proteins on recipient antigen-presenting cells. In this article, we present a description of each of these allorecognition pathways and discuss their role in acute and chronic rejection of allogeneic transplants.