After studying medicine in Paris, François moved to the New York University School of Medicine in 1962 as a postdoctoral fellow in the laboratory of Baruj Benacerraf. There he established that IgG1 (then known as γl) guinea pig antibodies were responsible for anaphylaxis sensitization, whereas the fixation of complement and the lysis of cells were exclusively the properties of γ2 (IgG2) antibodies. These results revealed for the first time that different biological properties could be assigned to distinct immunoglobulin isotypes. They led to the later demonstration that antibody heavy chains, and particularly their Fc fragments, contained sequences responsible for their biological properties. Upon his return to France at the Research Institute on Leukemias at Saint Louis Hospital in Paris, François, along with the hematologist Jean-Paul Lévy, focused on immune responses directed against leukemias caused by mouse retroviruses. The mouse major histocompatibility complex (H-2) had recently been linked to inherited susceptibility to some of those leukemias. In humans, an equivalent complex called HLA was just in the process of being dissected by Jean Dausset, also working at the Saint Louis Hospital. This led François and Dausset to analyze whether particular HLA alleles could account for susceptibility to certain cancers. In 1968, they published the first study comparing the distribution of the few known HLA alleles in patients suffering from acute leukemia and in unaffected controls, which did not demonstrate such connections in humans. Using antibody-induced redistribution of membrane antigens, François further established, with Catherine Neauport-Sautes, that the gene products from the D and the K ends of the H-2 region are expressed on independent molecules, an important finding at a time when molecular biological techniques had not become widespread among immunologists.
In the mid-1970s, together with Michel Fougereau, François established the first institute in France devoted exclusively to immunology and funded by the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Centre National de la Recherche Scientifique (CNRS). The Centre d'Immunologie de Marseille-Luminy opened in 1976 in Luminy, in southeast France. Although Luminy had the benefit of being (and indeed still is) one of the few pieces of pristine land on the Mediterranean coast, at that time, scientifically speaking, the campus was in the middle of nowhere. Considering the centralized nature of French institutions, very few people were betting on the success of a scientific operation developing so far away from Paris. The organization of the CIML, as established by its two founding fathers, was quite unusual in the French research landscape, which was dominated by large laboratories with many scientists working under the umbrella of a 'director for life'. Not only was the CIML headed by a rotating directorship, but it was composed of small, independent research teams revolving around core facilities operated by a dedicated technical staff. The new center grew rapidly, and its expansion included several groups headed by European and US scientists. Importantly, teams were nonpermanent and subjected to regular evaluation by a scientific advisory board composed primarily of foreign members, among whom luminaries such as Benacerraf, Cesar Milstein, Klaus Rajewsky and Max Cooper provided much insightful help. For the first ten years of the CIML's life, its scientific advisory board had to convene in an almost clandestine manner to avoid upsetting the sensitivities of French funding bodies and their then quite traditional, nationally based evaluation panels.
