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 β polypeptide chain (A_e) coded by a gene in the I-A subregion with a 32,000− to 35,000-dalton a chain (E_a) coded by a gene in the I-E subregion of the mouse H-2 gene complex. For expression of Ia.23, the A_e chain must be derived from the H-2^d haplotype (I-A^d), while the E_a can be provided by I-E^d, I-E^k, I-E^p, I-E^r, I-E^v, andI-E^w3, but not I-E^b, I-E^f, I-E^q, I-E^a, and I-E^u. With the exception of H-2^u haplotype, all Ia.7 (I-E)-positive haplotypes can provide the permissive E_a chain for generating Ia.23 by trans-complementation. In the H-2^d haplotype, Ia.23 is generated by cis-complementation of A^d with E^d. 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 la specificities expressed on the a or β chains (these could aid in the binding between the α and β chains such as la.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.