Beneficial Immunomodulation by Streptococcus mutans Anti-P1 Monoclonal Antibodies Is Fc Independent and Correlates with Increased Exposure of a Relevant Target Epitope

• Published in: The Journal of immunology (1950) 2009-10, Vol.183 (7), p.4628-4638
• Main Authors: Robinette, Rebekah A, Oli, Monika W, McArthur, William P, Brady, L. Jeannine
• Format: Article
• Language: English
• Subjects: Adhesins, Bacterial - administration & dosage; Adhesins, Bacterial - genetics; Adhesins, Bacterial - immunology; Agglutinins - immunology; Agglutinins - metabolism; Animals; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - therapeutic use; Bacterial Adhesion - genetics; Bacterial Adhesion - immunology; Binding Sites, Antibody; Epitopes - administration & dosage; Epitopes - genetics; Epitopes - immunology; Female; Genetic Predisposition to Disease; Humans; Immunoglobulin Fc Fragments - physiology; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Salivary Proteins and Peptides - immunology; Salivary Proteins and Peptides - metabolism; Streptococcus mutans - genetics; Streptococcus mutans - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0803300

We showed previously that deliberate immunization of BALB/c mice with immune complexes (IC) of the cariogenic bacterium Streptococcus mutans and mAbs against its surface adhesin P1 results in changes in the specificity and isotype of elicited anti-P1 Abs. Depending on the mAb, changes were beneficial, neutral, or detrimental, as measured by the ability of the serum from immunized mice to inhibit bacterial adherence to human salivary agglutinin by a BIAcore surface plasmon resonance assay. The current study further defined changes in the host response that result from immunization with IC containing beneficial mAbs, and evaluated mechanisms by which beneficial immunomodulation could occur in this system. Immunomodulatory effects varied depending upon genetic background, with differing results in C57BL/6 and BALB/c mice. Desirable effects following IC immunization were observed in the absence of activating FcRs in BALB/c Fcer1g transgenic mice. mAb F(ab')(2) mediated desirable changes similar to those observed using intact IgG. Sera from IC-immunized BALB/c mice that were better able to inhibit bacterial adherence demonstrated an increase in Abs able to compete with an adherence-inhibiting anti-P1 mAb, and binding of a beneficial immumomodulatory mAb to S. mutans increased exposure of that epitope. Consistent with a mechanism involving a mAb-mediated structural alteration of P1 on the cell surface, immunization with truncated P1 derivatives lacking segments that contribute to recognition by beneficial immunomodulatory mAbs resulted in an improvement in the ability of elicited serum Abs to inhibit bacterial adherence compared with immunization with the full-length protein.