The role of epitope specificity in the human opsonic antibody response to the staphylococcal surface polysaccharide poly N-acetyl glucosamine.
BACKGROUND
The staphylococcal surface polysaccharide poly N-acetyl glucosamine (PNAG) is a target for killing and protective antibody in animals. We investigated the human antibody response and specificity of binding and opsonic antibodies for different epitopes on PNAG in serum samples from patients with cystic fibrosis (CF) colonized and not colonized with Staphylococcus aureus.


METHODS
Serum samples from patients with CF colonized and not colonized with S. aureus were used to compare levels and specificities of binding and opsonic antibodies to native PNAG (>95% acetylation) and deacetylated PNAG (dPNAG, approximately 15% acetylation).


RESULTS
Colonized patients had higher killing activity mediated by opsonic antibody than did noncolonized patients in a PNAG-specific opsonophagocytic assay (P<.0001) but no difference in average levels of antibody to either PNAG or dPNAG by enzyme-linked immunosorbent assay. Killing activity in serum samples of the colonized patients correlated with the level of IgG specific to dPNAG more than to native PNAG. dPNAG and PNAG shared expression of the epitopes binding opsonic antibody, as evidenced by comparable inhibition of opsonophagocytic killing by both antigens. Affinity-purified antibodies specific to dPNAG were superior in mediating opsonic killing.


CONCLUSIONS
Human antibodies to PNAG that mediate opsonic killing bind primarily to the nonacetylated epitopes of this antigen, which indicates that these antigenic determinants are the dominant targets of the functional human antibody response to staphylococcal PNAG.
Kelly-Quintos
Casie
C
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. casie_kelly@student.hms.harvard.edu
Kropec
Andrea
A
Briggs
Stacy
S
Ordonez
Claudia L
CL
Goldmann
Donald A
DA
Pier
Gerald B
GB
D000117:Acetylglucosamine / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology / Q000382:microbiology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology; D013210:Staphylococcus / Q000276:immunology*
D000907:Antibodies, Bacterial; D000939:Epitopes; D009895:Opsonin Proteins; C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine