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A cluster of genes found in all mammals whose products are primarily responsible for the rapid rejection of grafts between individuals, immunological rejection, including interaction between lymphoid cells as well as between lymphocytes and antigen presenting cells. This region is called as major histocompatibility complex (MHC).
The T cell does not recognize antigen alone but in the context of the MHC molecules on the antigen-presenting cell. MHC contains three different classes of genes.
Within MHC three major sets of molecules are encoded:
Class I and II genes encode molecules involved in immunological recognition.
Class III genes encode some of the complement components concerned in the clevage of C3, a central event in the generation of an inflammatory response.
The MHC in mouse is the H-2 complex located in the middle portion of Chromosome 17. In man MHC is the HLA gene cluster on chromosome 6.
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Mouse MHC H-2 : Chromosome 17 ____________________________________________ K I S D Qa ____________________________________________
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Human HLA : Chromosome
6 _________________________________________________ D Class III B C A _________________________________________________
Class I antigen consists of one polypeptide chain (MW 45,000) non-covalently associated with another peptide, _2-microglobulin. _2-microglobulin is necessary for the expression of class I molecule.
Class II antigens consist of two polypeptide chains, the alpha chain and the beta chain.
Detection Serological Mixed leukocyte reaction
Distribution All nucleated cells B cells, macrophages and other APC's
Class I antigens are detected using a panel of known antibodies and complement to lyse donor lymphocytes; class II antigens are determined by the mixed leukocyte reaction using cultured cells.
Cytotoxic T cells (Tc) kill virus-infected target cells and foreign tissue grafts by recognizing class I antigens on those cells. Virus infected cells display viral antigens on their membranes which are recognized by cytotoxic cells.
Helper T cells (TH) recognize foreign antigen in association with class II molecules on the antigen presenting cells (APC).
Since MHC antigens are detected easily on leukocytes they are denoted by the initials of the species followed by LA (leukocyte antigen).
Main function of MHC is to regulate immune response. It may also be involved in susceptibility to diseases.
Self/non-self recognition systems of different animals are all different, though working on the same principle. Since the immune system of each individual animal is different, the "perfect pathogen" cannot evolve to spread through a population. Despite this, it is now known that possession of particular MHC antigens renders that animal more susceptible to particular diseases.
Examples:
Chickens homozygous for B1 or B4 haplotypes are more susceptible to autoimmune thyroiditis.
Selection for specific histocompatibility antigens has great potential for use in the genetic selection of disease-resistant strains of domestic animals.
The fate of a transplanted organ depends on transplantation antigens which are controlled by the MHC.
Initially, vascularization of graft is good, but in 11-14 days there is mononuclear cell infiltration, marked reduction in circulation, and eventual necrosis.
Antibody plays lesser role than cell-mediated immunity. As a result of an allograft transfer, small amounts of antibody bind to vessel walls and fix complement. Results in endothelial damage and release of chemotatic factors with PMN attraction.
T cells mainly responsible for graft rejection. Other inflammatory cells enter the rejection site. Rejection may involve both a delayed-type hypersensitivity response as well as action by cytotoxic T cells.
Carried with grafted tissue play a major role in the regulation of tissue immunogenicity by acting as stimulator cells to activate recipient T cells and cytotoxic T cells.
Immunologic reaction directed against host transplantation antigens. Severity of the reaction is related to the degree of genetic disparity between donor and host and the dose of inoculated immunologically competent lymphoid cells.
It appears that a prime biological function of the MHC is to participate in all immune responses mediated by T lymphocytes. The recognition of foreign cells by T cells is restricted. The T lymphocyte can only recognize a foreign antigen in the context of self MHC molecules inserted in cells. It is suspected that diseases of unknown etiology and some induced by viral infections occur only in genetically susceptible individuals.
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TV-281. Transplantation Immunity.
AV/AT Laboratory.
