Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 38, Pages 15051-15056Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0706028104
Keywords
immune evasion; mucosal immunity; antibody; Fc receptor; staphylococcal superantigen-like
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Infection by Staphylococcus aureus can result in severe conditions such as septicemia, toxic shock, pneumonia, and endocarditis with antibiotic resistance and persistent nasal carriage in normal individuals being key drivers of the medical impact of this virulent pathogen. In both virulent infection and nasal colonization, S. aureus encounters the host immune system and produces a wide array of factors that frustrate host immunity. One in particular, the prototypical staphylococcal superantigen-like protein SSL7, potently binds IgA and C5, thereby inhibiting immune responses dependent on these major immune mediators. We report here the three-dimensional structure of the complex of SSL7 with Fc of human IgA1 at 3.2 angstrom resolution. Two SSL7 molecules interact with the Fc (one per heavy chain) primarily at the junction between the C alpha 2 and CA domains. The binding site on each IgA chain is extensive, with SSL7 shielding most of the lateral surface of the CA domain. However, the SSL7 molecules are positioned such that they should allow binding to secretory IgA. The key IgA residues interacting with SSL7 are also bound by the leukocyte IgA receptor, Fc alpha RI (CD89), thereby explaining how SSL7 potently inhibits IgA-dependent cellular effector functions mediated by Fc alpha RI, such as phagocytosis, degranulation, and respiratory burst. Thus, the ability of S. aureus to subvert IgA-mediated immunity is likely to facilitate survival in mucosal environments such as the nasal passage and may contribute to systemic infections.
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