Hybrid IgA2/IgG1 Antibodies with Tailor-Made Effector Functions

Immunoglobulin (Ig) A and IgG are the principal immune effector molecules at mucosal surfaces and in blood, respectively. Mucosal IgA is polymeric and bound to secretory component, whereas serum IgG is monomeric. We have now produced IgA2/IgG1 hybrid antibodies that combine the properties of IgA and IgG. Antibodies with Cα3 at the end of the IgG H chain resemble IgA and form polymers with J chain that bind the polymeric Ig receptor. Like IgG, the hybrid proteins activated complement and bound FcγRI and protein A. Though the hybrid proteins contained both Cγ2 and Cγ3, they have a short in vivo half-life. Surprisingly, this decreased half-life correlated with a higher avidity than that of IgG for murine FcRn. Interestingly, antibodies with Cα1 replacing Cγ1 were resistant to extremes of pH, suggesting that Cα1 increases antibody stability. These results provide insights into engineering antibodies with novel combinations of effector functions.