* Transplantation of tissues from one individual to a genetically nonidentical recipient leads to a specific immune response called rejection that can destroy the graft. The major molecular targets in allograft rejection are allogeneic class I and class II MHC molecules.
* Allogeneic MHC molecules may be presented on donor APCs to recipient T cells (the direct pathway), or the alloantigens may be picked up by host APCs that enter the graft or reside in draining lymphoid organs and be processed and presented to T cells as peptides associated with self MHC molecules (the indirect pathway).
* The frequency of T cells capable of recognizing allogeneic MHC molecules is very high, explaining why the response to alloantigens is much stronger than the response to conventional foreign antigens. The reasons for this high frequency are an inherent bias of T cells to recognize MHC molecules and because many different T cell clones specific for different foreign peptides plus self MHC molecules may cross-react with an individual allogeneic MHC molecule.
* Graft rejection is mediated by T cells, including CTLs that kill graft cells and helper T cells that cause cytokine-mediated inflammation resembling DTH reactions, and by antibodies.
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Immunosuppression and Tolerance Induction to Allografts
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