Variable region identical IgA and IgE to Cryptococcus neoformans capsular polysaccharide manifest specificity differences [Protein Structure and Folding]

March 16th, 2015 by Janda, A., Eryilmaz, E., Nakouzi, A., Pohl, M. A., Bowen, A., Casadevall, A.

In recent years several groups have shown that isotype switching from IgM to IgG to IgA can affect the affinity and specificity of antibodies (Abs) 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 (NMR) with 15Nlabeled 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 epsilon 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 alpha and epsilon C regions affects their function and contributes to the special properties of those isotypes.
  • Posted in Journal of Biological Chemistry, Publications
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