Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism. T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells. Histocompatibility testing is most relevant for topics related to whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant. The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult.
Discovery The discovery of the MHC and role of histocompatibility in transplantation was a combined effort of many scientists in the 20th century. A genetic basis for transplantation rejection was proposed by C.C. Little and Ernest Tyyzer in a 1914 Nature paper; they showed that tumors transplanted between genetically identical mice grew normally, but those transplanted between non-identical mice were rejected and failed to grow. The role of the immune system in transplant reject was proposed by Peter Medawar, whose skin graft transplants in World War II victims showed that skin transplants between individuals had much higher rejection rates than self-transplants within an individual, and that suppressing the immune system delayed skin transplant rejection. Medawar shared theNobel Prize in Physiology or Medicine of 1960 in part for this work. In the 1930s and 1940s, George Snell and Peter Gorer individually isolated the genetic factors that when similar allowed transplantation between mouse strains, naming them H and antigen II respectively. These factors were in fact one and the same, and the locus was named H-2. Snell coined the term "histocompatibility" to describe the relationship between the H-2 cell-surface proteins and transplant acceptance. The human version of the histocompatibility complex was found by Jean Dausset in the 1950s, when he noticed that recipients of blood transfusions were producing antibodies directed against only the donor cells. The target of these antibodies, or the human leukocyte antigens (HLA), were discovered to be the human homologue of Snell and Gorer's mouse MHC. Snell, Dausset and Baruj Benacerraf shared the 1980 Nobel Prize for the discovery of the MHC and HLA.
Major histocompatibility complex (MHC)
HLA, the human form of the major histocompatibility complex (MHC), is located on chromosome 6 at 6p21.3. Individuals inherit two different HLA haplotypes, one from each parent, each containing more than 200 genes relevant to helping the immune system recognize foreign invaders. These genes include MHC class I and class II cell-surface proteins. MHC Class I molecules—HLA-A, HLA-B, and HLA-C—are present on all nucleated cells and are responsible for signaling to an immune cell that an antigen is inside the cell. MHC Class II molecules—HLA-DR, and HLA-DQ and HLA-DP—are only present on antigen presenting cells and are responsible for presenting molecules from invading organisms to cells of the immune system. The MHC genes are highly polymorphic, with thousands of versions of the MHC receptors in the population, though any one individual can have no more than two versions for any one locus. MHC receptors are codominantly expressed, meaning all inherited alleles are expressed by the individual. The wide variety of potential alleles and multiple loci in the HLA allow for many unique combinations in individuals.
Role in transplantation
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