title: Variable Region Identical IgA and IgE to Cryptococcus neoformans Capsular Polysaccharide Manifest Specificity Differences.
abstract: In recent years several groups have shown that isotype switching from IgM to IgG to IgA can affect the affinity and specificity of antibodies sharing identical variable (V) regions. However, whether the same applies to IgE is unknown. In this study we compared the fine specificity of V region-identical IgE and IgA to Cryptococcus neoformans capsular polysaccharide and found that these differed in specificity from each other. The IgE and IgA paratopes were probed by nuclear magnetic resonance spectroscopy with (15)N-labeled peptide mimetics of cryptococcal polysaccharide antigen (Ag). IgE was found to cleave the peptide at a much faster rate than V region-identical IgG subclasses and IgA, consistent with an altered paratope. Both IgE and IgA were opsonic for C. neoformans and protected against infection in mice. In summary, V-region expression in the context of the ϵ constant (C) region results in specificity changes that are greater than observed for comparable IgG subclasses. These results raise the possibility that expression of certain V regions in the context of α and ϵ C regions affects their function and contributes to the special properties of those isotypes.
authors.affiliation: From the Department of Microbiology and Immunology of the Albert Einstein College of Medicine, Bronx, New York 10461 and.
authors.forename: Alena
authors.initials: A
authors.lastname: Janda
authors.affiliation: Biotherapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
authors.forename: Ertan
authors.initials: E
authors.lastname: Eryilmaz
authors.affiliation: From the Department of Microbiology and Immunology of the Albert Einstein College of Medicine, Bronx, New York 10461 and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Nakouzi
authors.affiliation: From the Department of Microbiology and Immunology of the Albert Einstein College of Medicine, Bronx, New York 10461 and.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Pohl
authors.affiliation: From the Department of Microbiology and Immunology of the Albert Einstein College of Medicine, Bronx, New York 10461 and.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bowen
authors.affiliation: From the Department of Microbiology and Immunology of the Albert Einstein College of Medicine, Bronx, New York 10461 and arturo.casadevall@einstein.yu.edu.
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000918:Antibody Specificity; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology; D003455:Cryptococcus neoformans / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D007070:Immunoglobulin A / Q000737:chemistry*; D007073:Immunoglobulin E / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D010455:Peptides; D011134:Polysaccharides; D007073:Immunoglobulin E; C027478:glucuronoxylomannan
keywords: Antibody; Antigen; Immunoglobulin A (IgA); Immunoglobulin E (IgE); Isotype; Nuclear Magnetic Resonance (NMR); Peptides