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 the respiratory tract with IgA in comparison to other isotypes. Monoclonal IgA-isotype-switch variants were isolated from different IgG-producing hybridoma clones specific for surface epitopes of bacterial respiratory tract pathogens. Analysis of the molecular form of the IgA variants revealed the simultaneous production of monomeric, dimeric and higher polymeric IgA by a single-cell line with predominance of the polymeric forms. The specificities of the IgA variants were identical to the parent IgG antibodies as demonstrated by inhibition experiments. The IgA variant antibodies were separated into monomers and polymers by gel filtration. Intravenous injection of the different molecular forms of IgA and of IgG into mice were used to investigate the transport characteristics of IgA into murine upper and lower respiratory tract secretions by the physiological route in comparison to IgG. Polymeric IgA variant, monomeric IgA variant and IgG were detected in immunologically active form in both nasal secretion and bronchoalveolar fluid as evidenced 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 determined in secretions. Comparison of the secretion to serum transport ratios clearly indicates selective transport of polymeric IgA variant into nasal secretions relative to IgG parent antibody. Molecular and functional characteristics of the IgA variants make them ideal for passive mucosal immunization experiments and identification of protective epitopes in mucosal immunity.
Institute of Medical Microbiology, Hannover Medical School, Germany.
I
I
Steinmetz
F
F
Albrecht
S
S
Häussler
B
B
Brenneke
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001692:Biological Transport; D002460:Cell Line; D005260:Female; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011550:Pseudomonas aeruginosa / Q000276:immunology; D012137:Respiratory System / Q000276:immunology*
D000942:Antigens, Bacterial; D000954:Antigens, Surface; D007070:Immunoglobulin A; D007074:Immunoglobulin G