| MadSci Network: Immunology |
Cell surface markers play an extremely important role in organ transplantation. If all markers are identical between donor and recipient, the graft will be seen as “self” by the recipient’s immune system and accepted. This situation rarely exists except in the case of transplants between identical twins. Some cell surface proteins are polymorphic (= many forms), having slightly different amino acid sequences in different individuals. Such differences are recognized by the recipient’s immune system, and the “non-self” organ transplant is destroyed by T lymphocytes. The major histocompatibility complex (MHC) is called that because this group of proteins is the most important determinant of acceptance or rejection (except for blood group antigens – see below). MHC proteins are very polymorphic, so the chances of finding a perfect match are poor, and they are also easily recognized by T lymphocytes. This combination of factors makes them very strong transplantation antigens and MHC mismatched organs will be rejected.
Given these observations, your question of how organ transplants can be successful is a good one. With a large enough pool of potential organ donors, it is possible to find a match for many, but usually not all, MHC proteins. The success of modern organ transplantation is primarily due to the use of very powerful immunosuppressive drugs like cyclosporin. These drugs prevent the T lymphocytes of the recipient from responding to the non-self MHC proteins on the transplanted organ.
Another group of crucial cell surface markers is the ABO blood group antigens. These antigens are the result of carbohydrate modifications of lipids and are best known for their importance in another type of transplantation, the blood transfusion. However, blood group antigens are found on many cell types besides red blood cells. Type O individuals have antibodies to A and B antigens, type A have antibodies to B, and type B have antibodies to A, even if they have never had a blood transfusion. If an organ transplant is attempted from a type AB donor to a type O recipient, the antibodies will destroy the organ. The rejection will occur within hours, as opposed to the rejection by T lymphocytes, which takes weeks or months depending on the extent of MHC mismatch. Immunosuppressive drugs do not help in this situation, since the antibodies have already been produced.
Matching of blood group antigens and as many MHC proteins as possible are standard criteria in choosing donor/recipient combinations.
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