Expression of MHC class II A alpha k transgene. Pairing with endogenous beta-chain is dependent upon affinity and...

Studies on cell lines transfected with MHC class II genes have revealed important limitations on the assembly of haplotype-mismatched A alpha/A beta complexes. We have investigated pairing restriction in vivo by analyzing transgenic mice that carry an A alpha k gene on several H-2 haplotypes. Previously, we reported the A alpha k transgenic expression on the cell surface of H-2b and H-2u strains. Further transcomplementation studies performed with high A alpha k-expressing transgenic lines revealed that A alpha k chain can pair with A beta b,s,f,d,v, or u chains but not with A beta q. Homozygosity for the A alpha k transgene increased the expression of mixed heterodimers. The inefficient assembly of haplotype-mismatched class II polypeptides results from their inability to compete with the matched pairs. The higher affinity between the matched pairs can be overcome by increased synthesis of the mismatched pair. Thus, there is no "strict" sequence-based restrictions on pairing.