HLA system in solid organ transplantation part 4

histocompatibility testing


Transplanted foreign organs are inherently immunogenic to genetically different recipient individuals and inexorably succumb  to rejection. These transplants are referred to as allogenic, while transplants performed between individuals genetically identical, so-called syngeneic (eg identical twins), can be accepted indefinetely in the absence of immunosuppression. Both the relative immunogenicity of the transplant tissue  from the donor (being either foreign or self), and the discriminatory capacity and response to it by the recipient immune system (rejection vs acceptance), are in great part conferred  genetically within a set of loci referred to as the major histocompatibility complex (MHC). This genetic loci received its name after being identified as the crucial determinant for rejection of transplanted tumours in mice, though it was later identified to be responsible for conferring the capacity  to respond  immunologically to environmental antigens. In fact, the actual role of the MHC genes and molecules is to signal the presence of foreign invading elements or altered self-components to the immune system and to stimulate the activation of T cells to orchestrate the elimination of these infective organisms or the abnormal, potential cancerous cells. MHC molecules are expressed on the surface of cell, where they serve as the antigen-presentation cards to T cells. MHC molecules possess a binding groove  in their apical  portion that can bind  different distincts sets and sizes of antigenic peptides, and only bound peptides to MHC molecules are recognisable by the immune receptors of T cells. Thus, the set of inherited MHC genes by an individual determines his/her potential to respond to environmental antigens and its capacity to stimulate T cells.


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