Allorecognition

The strongest alloreaction is directed against incompatible molecules encoded by the Major Histocompatibility Complex (MHC). This can be explained by the fact that these MHC molecules play a fundamental role in antigen presentation and are thus optimally shaped to be recognized by T cells. Furthermore, they are extremely polymorphic so that two individuals virtually always express a different set of MHC molecules.

Alloreactive T cells recognize alloantigens as foreign because the allelic variant of the polymorphic protein expressed by the stimulator is different from the one expressed by the responder.

The response is initiated by the stimulator APC expressing the alloantigens will prime the responder T cells. These T cells may attack the stimulator directly or help B cells to produce MHC-specific antibodies. Hence, whether the organ is rejected by alloantibodies or by cytotoxic T cells or whether the HSC transplanted patient is attacked by the donor T cells (GVHD), the response starts always with the activation of allogeneic T cells.

Three types of immune cells play a essential role in allorecognition:

T cells can recognize a major histocompatibilty molecules in different ways. T cells are also able to recognize allogeneic tissues that are HLA-identical but differ for minor histocompatibility antigens.

Alloreactive T cells can also help B cells to produce alloantibodies that play a crucial role in the rejection of organs.

Natural Killer cells can also recognize allogeneic cells that do not express the same MHC-molecules as the responder (missing self).

But even when the donor and the recipient express the same MHC molecules, the T cell may recognize minor histocompatibilty antigens that are different between donor and recipient.