MONOCLONAL IGA CLASS-SWITCH VARIANTS AGAINST BACTERIAL SURFACE-ANTIGENS - MOLECULAR-FORMS AND TRANSPORT INTO MURINE RESPIRATORY SECRETIONS

The present study describes a new model for passive immunization of th e respiratory tract with IgA in comparison to other isotypes. Monoclon al IgA-isotype-switch variants were isolated from different IgG-produc ing hybridoma clones specific for surface epitopes of bacterial respir atory tract pathogens. Analysis of the molecular form of the IgA varia nts revealed the simultaneous production of monomeric, dimeric and hig her polymeric IgA by a single-cell line with predominance of the polym eric forms. The specificities of the IgA variants were identical to th e parent IgG antibodies as demonstrated by inhibition experiments. The IgA variant antibodies were separated into monomers and polymers by g el filtration. Intravenous injection of the different molecular forms of IgA and of IgG into mice were used to investigate the transport cha racteristics of IgA into murine upper and lower respiratory tract secr etions by the physiological route in comparison to IgG. Polymeric IgA variant, monomeric IgA variant and IgG were detected in immunologicall y active form in both nasal secretion and bronchoalveolar fluid as evi denced by binding to their antigens in an enzyme-linked immunosorbent assay. The relative contribution of the specific exogenous monoclonal IgA and monoclonal IgG to total IgA and IgG, respectively, was determi ned in secretions. Comparison of the secretion to serum transport rati os clearly indicates selective transport of polymeric IgA variant into nasal secretions relative to IgG parent antibody. Molecular and funct ional characteristics of the IgA variants make them ideal for passive mucosal immunization experiments and identification of protective epit opes in mucosal immunity.