Abstract
Immunoglobulins (Igs) play critical roles in immune defence against infectious disease. They elicit potent elimination processes such as triggering complement activation and engaging specific Fc receptors present on immune cells, resulting in phagocytosis and other killing mechanisms. Many important pathogens have evolved mechanisms to subvert or evade Ig-mediated defence. One such mechanism used by several pathogenic bacteria features proteins that bind the Ig Fc region and compromise engagement of host effector molecules. Examples include different IgA-binding proteins produced by Staphylococcus aureus, Streptococcus pyogenes, and group B streptococci, all of which interact with the same interdomain region on IgA Fc. Since this region also forms the interaction site for the major human IgA-specific Fc receptor CD89, the bacteria are able to evade CD89-mediated clearance mechanisms. Similar disruption of Ig effector function by pathogen Ig-binding proteins is evident in other species. Remarkably, all the Ig- binding proteins studied in detail to date are seen to target the CH2–CH3 domain inter- face in the Ig Fc region, suggesting a common mode of immune evasion. A second Ig subversion mechanism that has evolved independently in numerous pathogens involves proteases that cleave Ig molecules within their hinge regions, uncoupling the antigen rec- ognition capability of the Fab region from clearance mechanisms elicited by the Fc region. The emerging understanding of the structural basis for the recognition of Igs as substrates for these proteases and as interaction partners for Ig-binding proteins may open up new avenues for treatment or vaccination.
Original language | English |
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Pages (from-to) | 1651-1658 |
Number of pages | 8 |
Journal | Biochemical Society Transactions |
Volume | 44 |
Issue number | 6 |
Early online date | 2 Dec 2016 |
DOIs | |
Publication status | Published - 15 Dec 2016 |
Keywords
- Immunoglobulins
- IgA
- IgG
- Bacterial proteases
- Immune evasion
- Ig-binding proteins
- Streptococci
- STAPHYLOCOCCUS-AUREUS
- IgA1 protease
ASJC Scopus subject areas
- General Immunology and Microbiology