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In January 1972, in Science, Baruj Benacerraf and Hugh McDevitt summarised their remarkable discovery of major histocompatibility complex (MHC)-related immune response genes1 (figure 1). To label their work as a paradigm shift in rheumatology is wholly appropriate.
In their essay, the authors wrote, ‘there is considerable reason to believe that this type of genetic control of specific immune responses may play an important role in susceptibility to a variety of diseases in both animals and man.’1 They specifically speculated about immune response genes and ‘the frequency of autoantibodies in a number of clinical diseases, such as rheumatoid arthritis, systemic lupus erythematosus, thyroiditis, and other autoimmune diseases’.1 The hypothesis that human leukocyte antigen (HLA) molecules (the human version of MHC) influence susceptibility to immune-mediated disease was validated about 15 months later by two independent studies, both showing that the HLA antigen now known as HLA-B27 profoundly affected susceptibility to ankylosing spondylitis.2 Benacerraf and McDevitt were writing in an era that preceded the conceptualisation of immune-mediated diseases as a spectrum ranging from truly autoimmune to autoinflammatory. Their essay went beyond autoimmunity by also recognising that MHC molecules could be exerting control over the immune response to a foreign antigen. For example, they cited work showing that mouse susceptibility to a leukaemia virus was under the control of the MHC.
The Nobel Prize in Physiology or Medicine in 1980 was awarded to Jean Dausset, George D Snell and Baruj Benacerraf. Dausset was the first to identify MHC molecules on cells in peripheral blood.3 Snell recognised the mouse MHC as early as 1951 for …
Handling editor Josef S Smolen
Contributors JTR conceived the idea for this report and wrote the first draft. TG created the figure. All authors contributed to the critical reading and revision of the report.
Funding This work was supported by NIH Grant NEI RO1 EY029266, NCATS KL2R002370 and P30 EY010572; the Oregon Health & Science University Department of Medicine Wheels Up Award; the Medical Research Foundation of Oregon; and donations from the Stan and Madelle Rosenfeld Family Trust, the Grandmaison Fund for Autoimmunity Research, the William and Mary Bauman Foundation, and Research to Prevent Blindness. TG is the recipient of the Jane Bruckel Early Career Investigator Award from the Spondylitis Association of America.
Competing interests JTR consults for Abbvie, Novartis, Gilead, UCB, Corvus, Revolo, Neoleukin, Santen, Affibody and Horizon. He receives grant support from Horizon, the Malassezia Foundation and Pfizer. He receives royalties from UpToDate. He serves on a data monitoring board for Celgene-BMS. MF consults for Revolo.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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