Genetic Control of Immune Response

Abstract

In 1962 Humphrey and McDevitt (quoted by McDevitt and Sela 1965) made an important chance observation. While studying immunogenicity of certain synthetic polypeptides prepared and analyzed by Sela and his colleagues (see Sela 1969 for a review), they found a marked quantitative difference between two rabbit strains (Sandylops and Himalayans) in the ability to form antibodies against these antigens. The difference suggested that the antibody response to synthetic polypeptides was genetically controlled. Intrigued by this possibility and at the same time realizing the disadvantages of genetic studies on outbred rabbits, McDevitt began a genetic analysis of immune response, employing inbred strains and congenic mouse lines. McDevitt and his colleagues were soon able to demonstrate that the antibody response to synthetic polypeptides was, indeed, genetically controlled and, moreover, that it was determined primarily by a single, autosomal dominant gene (or gene cluster), immune response-1 (Ir-1),¹ located within the H-2 complex. This was not the first report in the mouse to indicate that immune responsiveness was genetically controlled, but it was the first report to imply a relatively simple basis for genetic control. In all previous studies, the correlation between the responses of parents and offspring had been complex and difficult to interpret.