Immunology and the challenge of transplantation

Transplantation of tissues or organs between individuals who are not genetically related often leads to rejection by the recipient. The human genes responsible for this process are located on the short arm of the chromosome 6 and are called Major Histocompatibility Complex (MHC). Six main loci have been identified in the human MHC: HLA-A, HLA-B and HLA-C belong to the HLA class I, while HLA-DP, HLA-DQ and HLA-DR belong to HLA class II. The physiological function of MHC molecules is to present peptides to the T cells. Indeed, they are integral components of the ligands that recognise most T cells, since the receptor of the T cell (TCR) has specificity for complexes of foreign antigenic peptides, and self-MHC molecules. Thus the proteins of the MHC are responsible for the body being able to distinguish between its own and foreign cells, known as self-tolerance and consequently are the proteins which determine the evolution of transplants. The special case of foreign MHC antigen recognition is known as allorecognition and consists of the capacity of T cells to recognise peptide/MHC complexes with which they have not been in contact during the process of maturation in the thymus. There are two mechanisms of allorecognition, direct and indirect; both can lead to rejection of the transplant. Direct recognition prevails during the first few weeks or months after transplantation, and is caused by the APCs of the donor. These cells start disappearing from the transplanted organ and indirect recognition becomes important. There is evidence that the indirect pathway is sufficient to mediate both acute and chronic rejection. In this chapter we will describe fundamental aspects of the MHC system, as well as, specifically, its involvement in the allogenic response of the immune system against organ transplants.