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The idiotypic response to ferredoxin in mice Demetrick, Douglas James


These investigations define a new protein idiotypic system-:- that of Clostridium pasteurianum ferredoxin (Fd). Previous studies from our laboratory have shown that the response to Fd, a small, non-mammalian electron transport protein is controlled by H-2K/I-A linked loci in mice and is almost a unideterminant response in H-2[sup k] mice. Strains of mice varying in Igh, Igl, and H-2 loci were immunized with Fd. Their Fd-immune sera were tested by inhibition in the ELISA with four specific anti-(anti-Fd)- idiotypes produced in rabbits to the purified, pooled anti-Fd sera from four different strains of mice. Major idiotypes were observed reproducibly in the anti-Fd responses of AKR/J, RF/J, and B10.BR/SnJ mice, while the anti-A/J idiotype did not reproducibly inhibit a high frequency of A/J anti-Fd antisera. Significant differences were observed between the levels of inhibition of pooled or individually analyzed anti-Fd antisera from the same mice. Further experiments showed that anti-Fd antisera from B10.BR mice have a high frequency of cross-reactivity with AKR/J anti-Fd idiotypes as do RF/J, C58/J, C3H/HeJ and CBA/J antisera. C58/J, C57BR/cdJ, and RF/J antisera also cross-react significantly with A/J anti-Fd idiotypes. Curiously, A/J and AKR/J anti-Fd antisera are not inhibited with anti-RF idiotype, and AKR anti-Fd antisera are not inhibited with anti-B10.BR idiotype. The idiotype profile of monoclonal anti-Fd antibodies was studied. The results demonstrated interstrain idiotypic cross-reactivity that paralled the results obtained with the serum antibodies of the appropriate mouse strain. These data, with the data from experiments utilizing serum antibodies do not demonstrate a correlation between idiotypic cross-reactivity and Igh or Igl allotypes. H-2 genes were observed to vary the pattern of idiotype expression in BIO recombinant mice, but no correlation between H-2 genes and idiotype expression could be observed. These results demonstrate that the anti-Fd response in H-2 mice is very complex with many intra and interstrain cross-reactive idiotypic families. Confirmatory results from 2-D electrophoretic analyses show-the presence- of many light chains in the anti-Fd response: These data are discussed in the context of existing hapten, carbohydrate, and protein antigenic systems, as well as in the context of current theories of idiotypic structure and antibody cross-reactivity.

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