In vitro comparison of the biologic activities of monoclonal monomeric IgA, polymeric IgA, and secretory IgA.
Secretory IgA (S-IgA), a major humoral mediator of mucosal immunity, is a polymeric Ig containing an unusual extra polypeptide, secretory component (SC), added during transcytosis through epithelial cells. Polymeric S-IgA is more effective than monomeric IgA (mIgA) and IgG in neutralizing viruses. It is not known whether this increased efficacy is due solely to the polymeric structure of the molecule or whether SC itself makes S-IgA more efficient; a quantitative in vitro comparison of the biologic activities of S-IgA and pIgA has not been reported. We prepared purified pIgA and mIgA mAbs directed toward the H1 hemagglutinin of PR8 influenza virus and purified monoclonal S-IgA (made from monoclonal pIgA injected into a Lewis rat and collected as S-IgA from bile) and compared their abilities to carry out hemagglutination inhibition (HI) and neutralization of the infectivity of PR8 influenza virus in vitro. The polymeric Igs (pIgA and S-IgA) were 5 times more effective than mIgA in HI and 7 to 10 times more effective than mIgA in virus neutralization. Addition of SC to pIgA did not modify its ability to mediate HI and had only a minimal effect (S-IgA was 1.4 times more effective) on its ability to neutralize influenza virus in vitro. Trypsin preincubation partially abolished mIgA- or pIgA-mediated, but not S-IgA-mediated, viral neutralization. Thus, although S-IgA is more stable functionally than pIgA, the addition of SC does not influence, positively or negatively, the biologic activity associated with the Fab of S-IgA.
Renegar
K B
KB
Department of Microbiology, University of Alabama, Birmingham 35294, USA.
Jackson
G D
GD
Mestecky
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000502:physiology; D001666:Binding Sites, Antibody; D001704:Biopolymers / Q000276:immunology / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007070:Immunoglobulin A / Q000378:metabolism* / Q000502:physiology; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D009980:Influenza A virus / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D012635:Secretory Component / Q000276:immunology
D000911:Antibodies, Monoclonal; D001704:Biopolymers; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D012635:Secretory Component; C034639:polymeric IgA