VARIABLE REGION DOMAIN EXCHANGE INFLUENCES THE FUNCTIONAL-PROPERTIES OF IGG

In the present study we have characterized a family of anti-dansyl Abs with the variable region of the heavy chain on human C-kappa and the variable region of the light chain on different human gamma constant r egions (creating inside-out molecules), Although fully assembled molec ules were secreted, this variable region exchange slowed the kinetics of Ab assembly, Although the variable region exchange does not lead to a detectable change in the microenvironment of the combining site, it did alter the kinetic parameters of binding to immobilized Ag, slowin g both the on and off rates, When effector functions were evaluated, i nside-out IgG1 and IgG3 were more effective in complement-mediated cyt olysis than their wild-type counterparts, Variable region domain excha nge may be one approach to obtaining Abs of identical specificity with altered binding characteristics.