Polygenic Control of the Immune Response to F Antigen

The ability to produce an autoimmune response to F antigen in mice is under H-2-linked and non-H-2-linked Ir-gene control. There is an absolute requirement for a k allele at H-2K or I-A in order to produce antiF antibodies. Low and high responsiveness is controlled by a non-H-2-linked Ir gene which behaves in a similar fashion to Ir-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 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 showed--AKD2--behaves as an dominant higher responder. Genetic analysis showed that the presence of a K allele at H-2K or I-A, a non-H-2-linked Ir gene inherited from the AKR mice determined dominant responsiveness. No manipulation of the immune response or combination of genes converted nonresponders lacking a k 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.