Gene complementations to generate Ia antigens (Ia.23) on hybrid molecules

Abstract

Ia specificity 23 is a "combinatorial" antigen generated on a hybrid I region molecule, formed by the noncovalent binding of a 26,000- to 28,000-dalton beta polypeptide chain (Ae) coded by a gene in the I-A subregion with a 32,000- to 35,000-dalton alpha chain (E alpha) coded by a gene in the I-E subregion of the mouse H-2 gene complex. For expression of Ia.23, the Ae chain must be derived from the H-2d haplotype (I-Ad), while the E alpha can be provided by I-Ed, I-Ek, I-Ep, I-Er, I-Ev, and I-Ew3, but not I-Eb, I-Ef, I-Eq, I-Es, and I-Eu. With the exception of H-2u haplotype, all Ia.7 (I-E)-positive haplotypes can provide the permissive E alpha chain for generating Ia.23 by trans-complementation. In the H-2d haplotype, Ia.23 is generated by cis-complementation of Ad with Ed. Lymphocytes of F1 animals expressed two I-E subregion coded hybrid Ia specificities; one formed by cis-complementation and another by trans-complementation. It is postulated that such hybrid determinants are involved in the recognition and generation of immune response to antigens such as GL-Phe and cytochrome C where dual Ir gene control has been demonstrated. It is also suggested that there are two types of Ia specificities: (1) allotypic Ia specificities expressed on the alpha or beta chains (these could aid in the binding between the alpha and beta chains such as Ia.7); and (2) hybrid Ia specificities which are unique interaction determinants formed by the specific association of the alpha and beta chains (e.g., Ia.22,23). These interaction gene products may be involved in antigen recognition and presentation.