George Snell, at the Jackson Laboratory in Maine, identifies from the 1940s onward, through genetic experiments with mice, a set of genes responsible for the rejection of transplanted tissue between genetically distinct individuals, which he names the major histocompatibility complex. Jean Dausset, at the Pasteur Institute in Paris, discovers in 1958 the first antigen of this system in humans — the HLA system (human leukocyte antigen) — after observing that patients who had received multiple blood transfusions developed antibodies against specific markers present in other people's white blood cells. Baruj Benacerraf, a Venezuelan-born scientist who emigrated to the United States, demonstrates that these histocompatibility genes not only determine transplant rejection but more generally regulate how the immune system recognizes and responds to foreign substances, establishing the link between the HLA system and the general regulation of the immune response. Together, these three discoveries establish the scientific foundation that makes organ-transplant compatibility possible through prior HLA typing between donor and recipient, drastically reducing the risk of rejection, and are also fundamental to understanding the genetic susceptibility to numerous autoimmune diseases associated with specific HLA variants.