Alloreactivity

The alloimmune response between individuals genetically disparate for antigens encoded within the major histocompatibility complex (MHC) remains a substantial barrier to transplantation of solid organs, tissues, and hematopoietic stem cells. Alloreactivity has been an immunological paradox because of its apparent contradiction to the requirement of MHC restriction for the induction of normal T lymphocyte mediated immune responses. Through crystallographic analyses and experimental systems utilizing murine CD8⁺ cytolytic T cell clones, major advances have been achieved in understanding the molecular and structural basis of T cell receptor recognition of MHC–peptide complexes and the basis of T cell mediated alloreactivity. These studies have further provided an explanation for the relatively high frequencies of alloreactive T cells compared to the frequencies of T cells for microbial derived antigens.