Identification of a human immunodominant B-cell epitope within the immunoglobulin A1 protease of Streptococcus pneumoniae.
BACKGROUND
The 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.


RESULTS
An 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.


CONCLUSIONS
The 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.
De Paolis
Francesca
F
Kenton laboratories, Kenton Srl, Rome, Italy. francesca.depaolis@kenton.it
Beghetto
Elisa
E
Spadoni
Andrea
A
Montagnani
Francesca
F
Felici
Franco
F
Oggioni
Marco R
MR
Gargano
Nicola
N
D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology* / Q000302:isolation & purification; D007070:Immunoglobulin A / Q000378:metabolism; D019151:Peptide Library; D011008:Pneumococcal Infections / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology*; D013291:Streptococcus / Q000201:enzymology; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; D007070:Immunoglobulin A; D019151:Peptide Library; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase