Major Histocompatibility Complex - MHC in Transplant Rejection

MHC in Transplant Rejection

In a transplant procedure, as of an organ or stem cells, MHC molecules act themselves as antigens and can provoke immune response in the recipient—thus transplant rejection. MHC molecules were identified and named after their role in transplant rejection between mice of different strains, though it took over 20 years to clarify MHC's role in presenting peptide antigens to cytotoxic T lymphocytes (CTLs).

Each human cell expresses six MHC class I alleles (one HLA-A, -B, and -C allele from each parent) and six to eight MHC class 2 alleles (one HLA-DP and -DQ, and one or two HLA-DR from each parent, and combinations of these). The MHC variation in the human population is high, at least 350 alleles for HLA-A genes, 620 alleles for HLA-B, 400 alleles for DR, and 90 alleles for DQ. Any two individuals not identical twins express differing MHC molecules. All MHC molecules can mediate transplant rejection, but HLA-C and HLA-DP, showing low polymorphism, seem least important.

When maturing in the thymus gland, T lymphocytes are selected for their T cell receptors (TCR) incapacity to recognize self antigens. Yet T lymphocytes can react against the donor MHC's peptide-binding groove, the variable region of MHC holding the presented antigen's epitope for recognition by TCR, the matching paratope. T lymphocytes of the recipient take the incompatible peptide-binding groove as nonself antigen. The T lymphocytes' recognition of the foreign MHC as self is allorecognition.

Transplant rejection has two types known as mediated by MHC (HLA):

• Hyperacute rejection occurs when, before the trasplantation, the recipient has preformed anti-HLA antibodies, perhaps by previous blood transfusions (donor tissue that includes lymphocytes expressing HLA molecules), by anti-HLA generated during pregnancy (directed at the father's HLA displayed by the fetus), or by previous transplantation;

• Acute humoral rejection and chronic disfunction occurs when the recipient's anti-HLA antibodies form directed at HLA molecules present on endothelial cells of the transplanted tissue.

In either situation, immunity is directed at the transplanted organ, sustaining lesions. A cross-reaction test between potential donor cells and recipient serum seeks to detect presence of preformed anti-HLA antibodies in the potential recipient that recognize donor HLA molecules, so as to prevent hyperacute rejection. In normal circumstances, compatibility between HLA-A, -B, and -DR molecules is assessed. The higher the number of incompatibilities, the lower the five-year survival rate. Global databases of donor information enhance the search for compatible donors.