Polygenic control of the immune response to F antigen

The ability to produce an autoimmune response to F antigen in mice is underH-2-linked and non-H- 2-linkedIr-gene control. There is an absolute requirement for ak allele atH-2K orI-A in order to produce anti-F antibodies. Low and high responsiveness is controlled by a non-H-2-linkedIr gene which behaves in a similar fashion toIr-3, in that as the dose of F-antigen is lowered, low responders behave as high responders and vice versa. This conversion from low to high responsiveness also occurs within a month after ATX.— Most F₁ hybrids derived from (responder x nonresponder) parents bearing identical F-types behave as dominant nonresponders. As a result of ATX, such F₁ mice convert to high responders. This conversion occurs if the animals are not immunized before day 90. If they receive F antigen prior to that time, they remain nonresponders for 7–9 months. One F₁ combination — AKD2 — behaves as a dominant high responder. Genetic analysis showed that in the presence of ak allele atH-2K orI-A, a non-H-2-linkedIr gene inherited from the AKR mice determined dominant responsivenss. No manipulation of the immune response or combination of genes converted nonresponders lacking ak allele into responders. Such complex genetic control suggests regulation by a number of independently segregating loci whose function it is to limit the autoimmune response to F antigen.