Evidence for homologues of the murine I-A and I-E loci in the rat MHC.

Various anti-Ia mouse alloantisera were examined for cross-reactivity with rat lymphocytes. Many of them were found to cross-react with rat spleen cells with anti-Ia-type (40 to 60%) killing. Likewise, mouse antisera raised against rat lymphocytes cross-reacted with mouse cells, and some of these reactions could be mapped within the I-A subregion and some within the I-E/C subregion of the mouse H-2 complex. Using such cross-reactive mouse alloantisera and a defined anti-MHC rat alloantiserum (BN anti-LEW), SDS-PAGE analyses were performed on an NP-40 extract of internally labeled LEW antigen. The cross-reactive mouse alloantisera precipitated Ia-like glycoproteins (35,000 and 28,000 m.w.), which could be completely removed by pretreatment with the rat anti-MHC antiserum. The cross-reactive anti-I-A and anti-I-E/C mouse antibodies were found to react with 2 different classes of rat Ia molecules by sequential precipitation analysis. On the basis of the specificity of the mouse alloantibodies, one Ia molecule appears to be a homologue of the murine I-A antigens and the other a homologue of the murine I-E antigens. Preabsorption of LEW antigen with cross-reactive anti-I-A and anti-I-E/C mouse alloantibodies together did not leave a detectable amount of residual Ia molecules precipitable with the rat alloantiserum, which indicates that there is probably no other major class of rat Ia molecules. These results support the hypothesis that these 2 major classes of Ia molecules have evolved independently from distinct primordial genes.