Human leukocyte antigen system and the immune response to it

Immunologic rejection of tissue grafts follows recognition of donor alloantigens; either those resulting from ABO incompatibility of those encoded by the human major histocompatibility complex, HLA. Alloantigens encoded by HLA are present on membrane proteins that are expressed constitutively by tissues or whose expression can be induced by cytokines released during inflammation. Genes of the HLA complex are highly polymorphic resulting in variations in amino acid sequence that shape the peptide binding pocket of HLA molecules and define the complementary structure that interacts with the T lymphocyte receptor for antigen. Variants of HLA proteins expressed by the allografts that are not expressed by the recipient can stimulate the immune response to the allograft resulting in rejection both by humoral antibody and through attack by T lymphocytes. Class II HLA antigens on donor cells can stimulate these responses directly by contact with recipient T cells. However, rejection also may result when HLA antigens are released from the graft, processed to peptides, and presented to recipient T cells by cells expressing recipient HLA Class II molecules. Rejection can be avoided by preventing activation of T lymphocytes, by minimizing differences in HLA proteins between recipient and donor or by avoiding preexisting responses to donor HLA antigens.