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 causing 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.
Any two individuals who are not identical twins will express differing MHC molecules. When maturing in the thymus, T lymphocytes are selected for their 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.
In all of the above situations, 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. The higher the number of incompatibilities, the lower the five-year survival rate.
Global databases of donor information enhance the search for compatible donors.
To clarify the usage, some of the biomedical literature uses HLA to refer specifically to the HLA protein molecules and reserves MHC for the region of the genome that encodes for this molecule, but this is not a consistent convention. MHC alleles are expressed in codominant fashion. The set of alleles that is present in each chromosome is called the MHC haplotype.
In humans, each HLA allele is named with a number. Each heterozygous individual will have two MHC haplotypes, one each from the paternal and maternal chromosomes.
The MHC genes are highly polymorphic; many different alleles exist in the different individuals inside a population. The polymorphism is so high, in a mixed population non endogamic , no two individuals have exactly the same set of MHC molecules, with the exception of identical twins. The polymorphic regions in each allele are located in the region for peptide contact. Of all the peptides that could be displayed by MHC, only a subset will bind strongly enough to any given HLA allele, so by carrying two alleles for each gene, a much larger set of peptides can be presented.
On the other hand, inside a population, the presence of many different alleles ensures there will always be an individual with a specific MHC molecule able to load the correct peptide to recognize a specific microbe. The evolution of the MHC polymorphism ensures that a population will not succumb to a new pathogen or a mutated one, because at least some individuals will be able to develop an adequate immune response to win over the pathogen.
The variations in the MHC molecules responsible for the polymorphism are the result of the inheritance of different MHC molecules, and they are not induced by recombination , as it is the case for the antigen receptors. Because of the high levels of allelic diversity found within its genes, MHC has also attracted the attention of many evolutionary biologists. From Wikipedia, the free encyclopedia.
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Types of MHC:
Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Main article: MHC class I. Main article: MHC restriction. Main article: Major histocompatibility complex and sexual selection. See also: Interpersonal compatibility. Main article: Human leukocyte antigen.
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Major Histocompatibility Complex
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Cellular peptide composition governed by major histocompatibility complex class I molecules
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September Journal of Immunology. Immunology : lymphocytic adaptive immune system and complement. Cytokines Opsonin Cytolysin. Surface antigens. Arrestin Calgranulin Blood group antigens Cell adhesion molecules Differentiation antigens. Transmembrane receptors : immunoglobulin superfamily immune receptors. The HLA complex of genes is classified into three classes as follows:.
The heavy chain has a variable and constant region. The variable region is highly pleomorphic. The polymorphism of these molecules is important in the recognition of self and non-self.
Major histocompatibility complex (MHC): structure, types and functions
The constant region of the heavy chain binds with the CD8 proteins of the cytotoxic T cells. This peptide-binding groove is located on the top surface of the class I MHC molecule, and bind a peptide of 8 to 10 amino acids. Class I proteins are involved in graft rejection and cell-mediated cytolysis.