Ir gene control of carrier recognition. III. Cooperative recognition of two or more carrier determinants on insulins of different species.

Abstract

AbstractWhen crosses between different nonresponder strains to pig and bovine insulin were tested, some cases of complementation could only be achieved if one of the strains had C3H bavkgrounmd,e.g.(C3H.SW × C3H/He)F1 and (C57BL/6 × C3H/He)F1 show complementation, whereas (C57BL/10 × B10.BR)F1 do not.It is suggested that three genes are necessary for the complementation, two genes in the H‐2 region and an additional gene in the C3H bacjground. It was therefore supposed that this type of complementation might be due to a cooperative recognition byone of the parental strains. This possibitility was tested by coimmunization experiments performed with the parental strains C3H/He and C57BL/6.Insulin to which these strains respond (sheep or bovine insulin, respectively) was injected together with an excess of an insulin nonimmunogenic in the parental strins but immunogenic to the hybrids (pig insulin).It proved that under these conditions the response of C3H/He mice to sheep insulin was reduced by more than 90%, whereas C57BL/6 mice gave a normal response to bovine insulin. However, both strains were now able to respond to the pig insulin as shown bythe antibody production to fluoresceinthiocarbamyl groups coupled to pig insulin. This shows that the missing carrier determinant can be provided by a different molecule.The results are discussed in terms of a multideterminant recognition of the antigen at the carrier level. The recognition of each carrier determinant can be provided by a different molecule.