History and naming of human leukocyte antigens

Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The antigens were initially identified by categorizing and performing massive statistical analyses on interactions between blood types. This process is based upon the principle of serotypes. HLA are not typical antigens, like those found on surface of infectious agents. HLAs are alloantigens, they vary from individual to individual as a result of genetic differences. An organ called the thymus is responsible for ensuring that any t-cells that attack self proteins are not allowed to live. In essence, every individual's immune system is tuned to the specific set of HLA and self proteins produced by that individual. (For more information please see immune tolerance). Where this goes wrong is when tissues are transferred to another person. Since individuals almost always have different "banks" of HLAs, the immune system of the recipient recognizes the transplanted tissue as non-self and destroys the offending tissue. It was through the realization of this that HLAs were discovered.

The thought that the mammalian body must have some way of identifying introduced foreign particles first arose during World War II. Numerous theories were proposed and it wasn't until 1958 that the first of these identifying proteins was found. The first standardized naming system was established in 1968 by the WHO Nomenclature Committee for Factors of the HLA System. HLA research didn't heat up until the 1980s when a group of researchers finally elucidated the shape of the HLA-A*02 protein (just one of many specific HLA proteins). Even more recently, in 2010, the WHO committee responsible for naming all HLA proteins revised their standards for naming to introduce more clarity and specificity in the naming system. It started with a plane crash in the height of the London Blitz. The pilot suffered severe burns requiring skin grafts. However, at the time skin grafts were a risky business, often being rejected for unknown reasons. The search for a reason spanned the next four decades and in some areas is still continuing today.

Peter Medawar was a zoologist turned clinician, who specialized in burn trauma. A plane crash near his home changed the path of his career, turning his work with burns from mere academia to a full on quest to save lives. Medawar and a Scottish surgeon, Tom Gibson, were tasked with working the Burns Unit of the Glasgow Royal Infirmary. The first insight came when the pair decided to experiment, and grafted part of a wound with the patient's skin, and another part with skin from the patient's brother. Within days the skin grafts from the brother were completely destroyed. Successive skin grafts from the brother were destroyed even faster, a fact that gave them the evidence they needed to implicate the immune system. Medawar later repeated this experiment on rabbits and 625 surgeries later validated their initial conclusions. Medawar then set out in search of the reason why rabbits rejected non-self grafts.

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