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HLA (1968)

Jean Dausset was working in Paris in the 1950s and was one of several scientists who became fascinated with the difficulties of transplanting organs, notably kidneys, without them being rejected. In 1958 he discovered the first leucocyte antigen, which he named “MAC” after the initials of the first three donors whose reactions to Daussett’s testing proved he had found a new leucocyte antigen.

He then studied autoimmune diseases with patients who had undergone repeated blood transfusions. He found that the antibodies found in these patients proved to be of no significance at all when it came to auto-immune diseases, but instead were an important indicator of differences in the cell-membrane structure of white blood cells between blood donors and recipients.

He then moved on to work with women who had given birth several times, so-called multiparous women. Dausset was able to show that one single genetic system, localised on one of the 23 pairs of chromosomes, was responsible for determining these antigens. Dausset described the first antigen in 1965, which he named Hu-1, for human-transplant antigen, replacing the MAC name he had earlier devised. Then, in 1968, the WHO’s nomenclature committee formally named these new antigens human leucocyte antigens (HLAs).

The discovery had immense practical significance. Using the knowledge of HLA typing, it was possible to tissue match organ donors to recipients, increasing the possibility of a successful transplant without rejection. HLA typing has also been important for other spheres of research, such as anthropology and the study of human evolution. HLA is extremely polymorphic and allelic variation has resulted in numerous HLA specificities. Since the discovery of Dausset’s MAC antigen, the nomenclature committee has received submissions from and designated names to more than 14,000 different HLA alleles.

Over the last six decades, in addition to its immune-biological function, the immunology community has come to appreciate the clinical impact of the HLA complex, for example in ensuring successful solid organ and hematopoietic progenitor cell transplantation, and in both associated disease diagnosis and HLA mediated drug interactions. The discovery of the HLA system is now seen as one of the most important breakthrough of the past 60 years of immunology research.