Variable region-identical monoclonal antibodies of different IgG subclass directed to Pseudomonas aeruginosa...

Antibodies directed to polysaccharide (PS) antigens of bacteria are crucial to host immunity to infection. The isotypes of antibodies made to PS, however, are restricted primarily to IgM and IgG1 and IgG2 in man and to IgM and IgG3 in mice. Using sequential sublining and sib selection, an IgG1 murine monoclonal antibody that has variable regions identical to those of a parent IgG3 monoclonal antibody directed to the high-molecular-weight component of the O-specific side chain of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide was derived. These antibodies differed markedly in their antigen binding and effector functions. IgG3 was superior in binding to multivalent PS both in purified and whole bacterial form, fixation of the third component of complement to the bacterial surface, and opsonization of P. aeruginosa for uptake by both murine and human phagocytes. These data suggest that the IgG subclass of these murine anti-LPS antibodies is an important determinant of both avidity for multivalent antigen and biologic function.