Structural similarity between antigens and self molecules could be responsible for low antibody responses in different immunogenetic (IR-gene) systems. B10.M and B10.D2 strains are high responders, whilst A. Thy-1-1 mice are low responders, following primary immunization with ferritin in saline. Cross-reactivity between mouse-self antigens and ferritin was tested by antigen excess and radioimmunoassay techniques, using cells obtained from normal, unimmunized high- and low-responder mice, to compete for specific antibody. Low-responder A.Thy-1-1 mouse cells consistently displaced more anti-ferritin antibodies than did high-responder B10.M and B10.D2 mouse cells at varying antibody and cell concentrations and these differences were statistically significant (P less than 0.001). It is suggested that the responder status of different strains of mice, following primary immunization with ferritin in saline, could be explained by the degree of cross-activity between self determinants and antigen, such that low responders cross-react to a greater degree with the test antigen than do high-responder mice. A similar mechanism of cross-reactivity could operate in the pathogenesis of HLA-linked diseases.

SUMMARYImmunogenetic (IR‐gene) systems consist of animals showing different quantitative antibody responses when immunized with similar doses of a given antigen.Strains of animals giving high and low antibody titres are described as high and low responders, respectively.The degree of dominance in F1 hybrid strains, obtained from a cross between high and low responder parents, can readily be calculated using the dominance index formula, which takes the value of +1 for complete dominance, ‐1 for complete recessivity and the value of zero for no dominance.In reviewing 1527 F1 animals, obtained from ninety‐one immunogenetic systems, the degree of dominance (d) was found to be: + 0±0076 ± 0±1053 (mean ± s.e.), which is close to a value of zero and this is consistent with codominant inheritance.It is suggested that in immunogenetic systems, both alleles are expressed as co‐dominant genes.

The immune response to the antigen horse spleen ferritin, has been investigated in ten inbred parental strains and seven different F1 hybrid strains of mice, using an antigen excess technique. The degree of dominance in an F1 hybrid system can be estimated by using the Fisher dominance index. The responses in F1 hybrid animals, obtained from crosses of high and low responder parents, varied from dominant to recessive but the overall mean dominance index for the ferritin immunogenetic system was found to be -0.0467 +/- 0.0083 (mean +/- s.e.), a value close to zero, which suggests a codominant mode of inheritance of IR-genes to ferritin and this is consistent with most published data in other F1 IR-gene systems.