Abstract
BackgroundThe IgA1 protease of Streptococcus pneumoniae is a proteolytic enzyme that specifically cleaves the hinge regions of human IgA1, which dominates most mucosal surfaces and is the major IgA isotype in serum. This protease is expressed in all of the known pneumococcal strains and plays a major role in pathogen's resistance to the host immune response. The present work was focused at identifying the immunodominant regions of pneumococcal IgA1 protease recognized by the human antibody response.ResultsAn antigenic sequence corresponding to amino acids 420–457 (epiA) of the iga gene product was identified by screening a pneumococcal phage display library with patients' sera. The epiA peptide is conserved in all pneumococci and in two out of three S. mitis strains, while it is not present in other oral streptococci so far sequenced. This epitope was specifically recognized by antibodies present in sera from 90% of healthy adults, thus representing an important target of the humoral response to S. pneumoniae and S. mitis infection. Moreover, sera from 68% of children less than 4 years old reacted with the epiA peptide, indicating that the human immune response against streptococcal antigens occurs during childhood.ConclusionThe broad and specific recognition of the epiA polypeptide by human sera demonstrate that the pneumococcal IgA1 protease contains an immunodominant B-cell epitope. The use of phage display libraries to identify microbe or disease-specific antigens recognized by human sera is a valuable approach to epitope discovery.
Highlights
The immunoglobulin A1 (IgA1) protease of Streptococcus pneumoniae is a proteolytic enzyme that cleaves the hinge regions of human IgA1, which dominates most mucosal surfaces and is the major IgA isotype in serum
We isolated several antigenic regions of S. pneumoniae proteins by challenging a pneumococcal genome display library with antibodies from one patient infected by the bacterium [20]
We previously demonstrated the potential of phage-display technology in identifying B-cell epitopes recognized by the human immune response against Toxoplasma gondii and S. pneumoniae infection [20,28,29,30], even though such a technique usually favors the identification of linear epitopes whereas conformational epitopes are often overlooked
Summary
The IgA1 protease of Streptococcus pneumoniae is a proteolytic enzyme that cleaves the hinge regions of human IgA1, which dominates most mucosal surfaces and is the major IgA isotype in serum. This protease is expressed in all of the known pneumococcal strains and plays a major role in pathogen's resistance to the host immune response. Streptococcus pneumoniae is a human pathogen causing significant morbidity and mortality worldwide It is a transient member of the normal bacterial flora that colonizes the upper respiratory tract of the host being a major cause of various diseases such as otitis media, pneumonia, sepsis and meningitis. In the last decade there has been a great effort in developing improved vaccines to prevent pneumococcal disease
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