Structural polymorphism of I–E subregion antigens determined by a gene in the H–2K to I–B genetic interval

Abstract

THE generation of immune responses in mice is influenced by Ir genes located in the I region of the major histocompatibility complex (MHC)¹. In some instances maximum responses require complementation by two genes, one in the I–A or I–B and the other in the I–E or I–C subregion^2,3. The effects of these genes are thought to be mediated by Ia alloantigens, which are cell surface molecules whose expression is controlled by the I region⁴. This is based on the observations that anti-Ia sera inhibit in vitro immune responses^5,6, and soluble factors that enhance in vitro immune responses express Ia alloantigenic determinants^7,9. Jones et al.¹⁰, using two-dimensional gel electrophoresis, observed that the expression of I–E subregion antigens is controlled by two genes, one in the I–A subregion, the other in the I–E subregion, and that the polymorphism of these antigens is influenced by an I–A subregion gene. As an explanation, the authors proposed that only one of the two polypeptide chains present in I–E immunoprecipitates is an I–E subregion product, the second being a product of the I–A subregion. Antisera obtained by cross-immunisation of I–E subregion-disparate strains of mice immunoprecipitates a molecular complex consisting of two chains, designated α and β, with molecular weights of 32,000 and 29,000 respectively^11–14. Previous studies suggested that I–E antigens isolated from B10.A(5R) and B10.D2 mice had identical α-chains but different ^β-chains¹⁵. However, as these mice differed at multiple genetic regions, it was not possible to show which I subregion(s) determined the polymorphism of the E_β chain. Therefore, we investigated the effects of the I–A subregion on the polymorphism of I–E subregion antigens. We have now shown by peptide mapping that the I–E subregion polymorphism which Jones et al. found to be controlled by the I–A subregion probably reflects structural polymorphism of β-chains controlled by an I–A subregion gene.