Ia specificities 22 and 23 were found t o be determinants on hybrid Ia molecules, formed by the noncovalent binding of a 26,000-28,000 dalton beta polypeptide chain (A,) coded by the I-A subregion and a 32,000-35,000 dalton alpha chain (E,) coded by the I-E subregion. For expression of Ia.23 the A, chain, coded by the I-A subregion, must be derived from the H-2d haplotype, while Ab, A S , or A k can provide the complementing beta chain for the expression of Ia.22. For expression of Ia.22 and Ia.23, most Ia.7 positive strains can provide the Complementing alpha chain (Ea), with the one exception of B 1O.PL (Eu), which is Ia.7 positive but will not complement with Ad t o express Ia.23. Antisera were also produced against hybrid Ia antigens by immunizing with F1 cells expressing Ia.22 or Ia.23 generated by transcomplementation. These antisera detect the same specificities as conventional anti-Ia.22 and anti-Ia.23 sera produced against cis-complementing la antigens. It is postulated that hybrid Ia determinants are involved in recognition and generation of immune response t o antigens under dual Ir gene control. It is also suggested that there are 2 types of Ia specificities: 1) allotypic Ia specificities expressed on the alpha or beta chains (for example, Ia.7 on the E, chain) and 2) hybrid Ia specificities, which are unique interaction determinants formed by the association of alpha and beta chains (for example, Ia.22 and Ia.23). These interaction gene products may be involved in antigen recognition and presentation.
Key words: hybrid Ia antigens, dual gene control Ia antigens coded by the I-A and I-E subregions of the H-2 gene complex consist of 2 noncovalently associated polypeptides of 32,000-35,000 (alpha) and 26,000-28,000 (beta) daltons. Two-dimensional gel electrophoresis studies of Jones et a1 [l , 21 and tryptic peptide studies by Cook e t a1 [3,4] and Silver [ 5 ] have suggested that the I-E subregion molecule is formed by complementation of genes in the I-A subregion and I-E subregion, with the I-A subregion coding for the beta chain (A,) and the I-E subregion