The Genetic Basis of Transplant Rejection

Research that began in the 1940s gave geneticists the first hints that a portion of the mammalian genome contained a cassette of genes that governed the acceptance or rejection of transplanted tissues. This grouping of genes was labeled the major histocompatibility complex (MHC). Subsequently, it has been found that the MHC also contains genes that are genome the total genetic material in a cell or organism

Five "knockout" piglets, considered to be the first of their kind, were raised with the intention of using their organs for human transplants. Knockout pigs have the gene inactivated that usually leads human immune systems to rejecting pig organs.

antigen a foreign substance that provokes an immune response involved in governing antibody responses as well. MHC molecules are identical between identical twins, but are otherwise different for every individual. Thus they allow the body to distinguish "self" from "nonself" on the molecular level.

The immunogenicity (ability to induce an immune response) of major transplantation antigens is so strong that differences between the antigens of the donor and recipient is enough to trigger an acute rejection response. To the extent that it is possible, therefore, the recipient and donor are matched for MHC type, to minimize acute rejection.

However, there are cases in which the donor and recipient are very well matched, and yet rejection of the graft still occurs. This is due to other genes found in various places in the genome, known as minor histocompatibility genes, that encode for other weaker transplantation antigens, or foreign pep-tides, that can cause a chronic rejection response. Currently, researchers have not been able to determine the extent or location of all of these genes. Results obtained from the mapping of genes in the human genome will aid in overcoming this problem.

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