HLA antigens and tissue typing

Jean Dausset had worked at the regional blood transfusion center in Paris from 1944. After a postdoctoral year in Boston he tried to apply the new red cell methods, such as the antiglobulin test, to white blood cells in patients with leukopenia, and got no reaction. By chance he tested serum from a patient who had received many transfusions, a sample that had sat in the refrigerator, and it clearly agglutinated white cells from another person. He made this observation of leuko-agglutination in 1952.

In 1958, as head of the immunohematology laboratory at the National Blood Transfusion Centre, Dausset tested such sera against the white cells of a panel of people and described the first leukocyte antigen, which he called MAC and which is now HLA-A2. His paper, in French in Acta Haematologica, raised the role of these antigens in transplanting organs and tissues. The same year Rose Payne and, separately, Jon van Rood described women who had borne several children, never transfused, whose serum agglutinated white cells from the father, the children and some unrelated donors. Van Rood used a computer to sort the reactions into clusters. The geneticist Walter Bodmer, who worked with Payne, later wrote that MAC was only loosely related to HLA-A2 and that van Rood, more than Dausset, set the scene for the discovery of the system.

Bernard Amos started international histocompatibility workshops in 1964, and van Rood organized the second in 1965. That year Dausset, testing fifty sera against fifty people, showed a single system comparable to the mouse H-2 system, which he called Hu-1 and which was renamed HLA. Skin grafts among volunteers, carried out by Felix Rapaport of New York, tied graft survival to tissue incompatibility. Paul Terasaki's microcytotoxicity assay became the standard test for HLA types, and his data gave the most striking early link between HLA matching and graft survival.

The genes sit in a small region of chromosome 6. HLA typing came into use to match donors and recipients for kidney transplants and in disputed paternity cases, and certain types were tied to disease risk, such as HLA-B27 with ankylosing spondylitis. Dausset shared the 1980 Nobel Prize in Physiology or Medicine with George Snell and Baruj Benacerraf for discoveries about genetically determined cell surface structures that regulate immune reactions.