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Allorecognition refers to detection by the immune system of genetically encoded polymorphisms between members of the same species. Following transplantation of allogeneic tissues, recognition by recipient T lymphocytes of foreign proteins expressed by donor cells (T-cell allorecognition) initiates a cascade of immunological reactions resulting in rapid elimination of donor cells and rejection of the graft. Over the past three decades, T-cell allorecognition has represented a challenging enigma for cellular immunologists. Initial immunogenetics studies in transplanted individuals led to identification of proteins encoded with the major histocompatibility complex (MHC) locus as the main driving force behind allorecognitionl². It is now firmly established that this process is mediated via two distinct and non-exclusive mechanisms: thedirectandindirect allorecognitionpathways (Figure 8.1)³. In direct allorecognition …