Elicitation of the maternal antibody response to the fetus by a broadly shared MHC class I antigenic determinant.

The antibody response to the semiallogeneic fetus in the rat was examined in eight mating combinations that were chosen specifically to cross different major histocompatibility complex (MHC) and nonMHC loci. The BN X DA and BN X BN.1A(DA) matings (n anti-a) were the only ones to show an antibody response to the fetus, and the response occurred in 25-64% of the matings. All the other six mating combinations studied were negative by hemagglutination, cytotoxicity, and cellular radioimmunoassay. The response appeared in the postpartum period after the first litter and reached its maximal frequency during the postpartum periods of the second and third matings. There was no correlation between the litter size and the presence or absence of an antibody response to the fetal antigens. The antibodies elicited by the fetus were hemagglutinating but not cytotoxic, and consisted of only one isotype, IgG2a, whereas in the alloantiserum raised by skin grafting and the injection of lymphocytes, they were distributed among the IgG2a greater than IgG1 greater than IgM isotypes and were both hemagglutinating and cytotoxic. Using reciprocal congenic strains, the pregnancy-induced antibody response was shown to be against MHC antigens only. This finding was confirmed by testing the sera against rats from a population that was segregating for the haplotypes a/a, a/n, and n/n. Comparison of the pregnancy-induced antibody with the BN anti-DA alloantibodies by absorption studies showed that the former was less crossreactive, did not react with the RT1.Aa haplotype-specific antigenic determinant, and did react with an antigenic determinant shared among the a, d, o, i, e, f, r10, b, and m haplotypes--but not with the n, c, g, k, l, h, or u haplotypes. Using the DA.1I and r10 strains in cellular radioimmunoassay, absorption, and immunoprecipitation experiments, it was shown that the pregnancy-induced antibody was elicited by a class I antigenic determinant, provisionally designated Pa, which is encoded by a locus in the vicinity of RT1.A.