Cross-reactions of anti-I-Ek monoclonal antibodies with subsets of I-Ab molecules.
Monoclonal antibodies H9-15.4 and H39-459 were derived from an A.TH anti-A.TL immunization. Antibodies H9-15.4 and H39-459 were found to be directed against the I-Ek molecule with positive reactions against B10.A (AkEk) and B10.S(9R) (AsEk) but not B10.A(4R) (AkEb). The monoclonal antibodies were also found to react with the b and q haplotypes, which do not express an I-E molecule. Sequential precipitation analysis showed that in the b haplotype, H9-15.4 and H39-459 react with the I-Ab molecule. These results showed that H9-15.4 and H39-459 recognize determinants shared by I-Ek and I-Ab molecules, suggesting that I-A and I-E molecules may have a common evolutionary origin, possibly through gene duplication. Sequential immunoprecipitation analysis of I-Ab molecules precipitated by H9-15.4 and H39-459 also suggested that these monoclonal antibodies recognize subsets of I-Ab molecules. Pretreatment with the 17-227 monoclonal anti-I-Ab antibody (Ia.15) had no effect on I-Ab molecules precipitated by H9-15.4 and H39-459. Also, pretreatment with H9-15.4 and H39-459 had no effect on I-Ab molecules immunoprecipitated by 17-227. Also H9-15.4 and H39-459 only partially cleared Ia molecules immunoprecipitated by each other. These results suggest that 17-227, H9-15.4, and H39-459 detect a minimum of four subsets of I-Ab molecules. To account for these observations, it is proposed that during evolution of the mouse H-2 complex, in addition to gene duplication of ancestral gene(s) to yield the genes encoding E alpha A alpha, A beta, and E beta polypeptide chains, further gene duplication occurred, forming multiple copies of genes encoding each Ia polypeptide chain.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D011232:Chemical Precipitation; D003429:Cross Reactions; D005802:Genes, MHC Class II; D005815:Genetic Code; D006183:H-2 Antigens / Q000235:genetics; D006649:Histocompatibility Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000145:classification*; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen