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 β polypeptide chain (Ae) coded by a gene in the 1-A subregion with a 32,000- to 35,000-dalton α chain (Eα) 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 Eα 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-Ea, and I-Eu. With the exception of H-2u haplotype, all Ia.7 (I-E)-positive haplotypes can provide the permissive Eα 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 α or β chains (these could aid in the binding between the α and β chains such as Ia.7); and (2) hybrid Ia specificities which are unique interaction determinants formed by the specific association of the α and β chains (e.g., Ia.22,23). These interaction gene products may be involved in antigen recognition and presentation.
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