Derivation of a monoclonal antibody that detects an Ia antigen encoded by 2 complementing I-subregions.

A monoclonal antibody designated A303, which reacts with Ia antigens controlled by the complementation of 2 distinct I-subregion genes, is described. Complementation of both I-A and I-EC subregion gene products is necessary for the cytotoxic, direct and 125I-protein A-amplified indirect cell binding, and immunoprecipitation activities of A303. Positive prototype strains of independent origin include H-2k,p, whereas A303-negative haplotypes include H-2b,d,f,r,s,u. Seven recombinant strains, H-2ap5,as1,h4,i3,i5,t3,t4 representing intra I-region cross-over events between positive and negative haplotypes are A303 negative. Trans complementation occurs between the I-Ak allele and the I-EdCd, I-EkCk and I-EkCd alleles, respectively. Analysis of F1 heterozygotes suggests that A303-binding activity is also controlled by gene-dose effects. Thus, the activity of A303 is formally equivalent to a system of coupled complementation previously described for Ir and Is genes.