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J. Exp. Med., Volume 188, Number 7, October 5, 1998 1223-1229

Immunocytochemical Colocalization of Specific Immunoglobulin A with Sendai Virus Protein in Infected Polarized Epithelium

By Hisashi Fujioka,*Dagger Steven N. Emancipator,*Dagger Masamichi Aikawa,parallel Dennis S. Huang,Dagger Frank Blatnik,Dagger Tracy Karban,Dagger Kristin DeFife,Dagger and Mary B. MazanecDagger §

From the * Institute of Pathology, the Dagger  Department of Pathology and the § Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106; and parallel  The Institute of Medical Sciences, Tokai University, Boseidai, Isehara, Kanagawa 259-1193,  Japan

Immunoglobulin (Ig)A provides the initial immune barrier to viruses at mucosal surfaces. Specific IgA interrupts viral replication in polarized epithelium during receptor-mediated transport, probably by binding to newly synthesized viral proteins. Here, we demonstrate by immunoelectron microscopy that specific IgA monoclonal antibodies (mAbs) accumulate within Sendai virus-infected polarized cell monolayers and colocalize with the hemagglutinin- neuraminidase (HN) viral protein in a novel intracellular structure. Neither IgG specific for HN nor irrelevant IgA mAbs colocalize with viral protein. Treatment of cultures with viral-specific IgA but not with viral-specific IgG or irrelevant IgA decreases viral titers. These observations provide definitive ultrastructural evidence of a subcellular compartment in which specific IgA and viral envelope proteins interact, further strengthening our hypothesis of intracellular neutralization of virus by specific IgA antibodies. Our results have important implications for intracellular protein trafficking, viral replication, and viral vaccine development.

Key words: immunoglobulin A;  Sendai virus;  mucosal immunity;  colocalization;  hemagglutinin-neuraminidase protein


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