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The present work was focused at identifying the immunodominant regions of pneumococcal IgA1 protease recognized by the human antibody response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An antigenic sequence corresponding to amino acids 420\u2013457 (epiA) of the<jats:italic>iga<\/jats:italic>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<jats:italic>S. mitis<\/jats:italic>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<jats:italic>S. pneumoniae<\/jats:italic>and<jats:italic>S. mitis<\/jats:italic>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The broad and specific recognition of the epiA polypeptide by human sera demonstrate that the pneumococcal IgA1 protease contains an immunodominant B-cell epitope. 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