Characterization of the<i>Streptococcus mutans</i>P1 Epitope Recognized by Immunomodulatory Monoclonal Antibody 6-11A

Rhodin, Nikki R.; Cutalo, Jenny M.; Tomer, Kenneth B.; McArthur, William P.; Brady, L. Jeannine

doi:10.1128/iai.72.8.4680-4688.2004

Cited by 15 publications

(33 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elimination of this region destroyed or substantially decreased the binding of four anti-P1 MAbs that did not react with a recombinant P1 polypeptide encompassing the P region. It was subsequently shown by additive ELISA that the epitopes recognized by these MAbs were reconstituted by the interaction of discontinuous A region and P region polypeptides containing various degrees of flanking sequence (41,57). While the number of A and P region repeats within P1 homologs varies among strains and species, no Ag I/II family protein has been identified that completely lacks either of these two domains.…”

Section: Resultsmentioning

confidence: 99%

“…This is consistent with previous results that indicated that certain epitopes are masked or cryptic in the context of the complete unaltered sequence (41). MAbs 5-5D and 6-11A share the common properties of having their core epitopes reconstituted by an interaction of A and P region polypeptides, but unlike 4-10A, their binding as assessed by additive ELISA was enhanced by inclusion of sequence immediately upstream of the A region (41,57). These two MAbs again were similar to one another, and their binding improved as the number of reintroduced prolinerich repeats was increased.…”

mentioning

confidence: 98%

“…X-ray crystallography of the central portion of P1, including the variable region, revealed a flexible beta-sandwich placing the A region and P region into close proximity (67). Several studies have now shown that the A and P regions of P1 contribute to complex conformational epitopes recognized by anti-P1 monoclonal antibodies (MAbs), some of which can be reconstituted by the interaction of recombinant A and P region-containing polypeptides (41,57,58,60,69).In-frame deletion of either the A region (P1⌬A) or the P region (P1⌬P) of P1 results in a loss of surface-localized P1 on S. mutans, even when N-terminal signal and C-terminal anchor sequences are not altered (5, 60). Internally deleted molecules are not released into culture supernatants and are barely detectable in S. mutans cytoplasmic fractions, despite the presence of wild-type levels of spaP mRNA.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Requirements for Surface Expression and Function of Adhesin P1 from Streptococcus mutans

et al. 2008

Self Cite

View full text Add to dashboard Cite

In this report, we define requirements for the successful translocation and functional maturation of the adhesin P1 of Streptococcus mutans. Conformational epitopes recognized by anti-P1 monoclonal antibodies (MAbs) were further characterized, thus facilitating the use of particular MAbs as tools to monitor the locations of various forms of the protein. We show that correct localization of P1 is dependent on structural features of the molecule itself, including a requisite A region-P region intramolecular interaction that occurs within the cell prior to secretion. P1 also was shown to be affected by several members of the protein-foldingsecretion-turnover apparatus. It does not achieve a fully functional form in the absence of the trigger factor PPIase homolog RopA, and its translocation is delayed when DnaK levels are limited. In addition, dnaK message levels are differentially altered in the presence of P1 lacking the alanine-rich compared to the proline-rich repeat domains. Lastly, nonsecreted P1 lacking the P region accumulates within the cell in the absence of htrA, implying an intracellular HtrA protease function in the degradation and turnover of this particular internal-deletion polypeptide. However, the opposite effect is seen for full-length P1, suggesting a sensing mechanism and substrate-dependent alteration in HtrA's function and effect that is consistent with its known ability to switch between chaperone and protease, depending on environmental perturbations.Streptococcus mutans is an oral bacterium that is a major etiologic agent of dental caries (19). The multidomain (M r , ϳ185,000) wall-associated multifunctional fibrillar cell surface protein P1 (15), encoded by spaP (28, 33), was originally identified as antigen (Ag) I/II (59). It is also called PAc (48), encoded by pac (49), and is widely understood to enable attachment of S. mutans to the acquired salivary pellicle on teeth. Ag I/II family proteins are expressed by most oral streptococci and mediate interactions with salivary constituents; host cell matrix proteins, such as fibronectin, fibrinogen, and collagen; and other oral bacteria (reviewed in reference 26). They share architectural features with a broad category of surface adhesins prevalent among streptococci and staphylococci called microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), whose functions are dependent on complex structural elements (63). P1 contains a 38-residue amino-terminal signal sequence, a series of three 82-residue alanine-rich tandem repeats (A region); a 144-residue variable (V) region, where 20/36 amino acid differences between P1 and PAc are clustered (4); a central proline-rich (P) region, comprised of three 39-residue tandem repeats; and carboxy-terminal membrane-and wall-spanning regions, including the LPXTG motif characteristic of wall-anchored sortase substrates (14, 66). A schematic representation of the molecule and derivatives evaluated in this study is shown in Fig. 1.Several regions have been implicated in the ligand bindin...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Requirements for Surface Expression and Function of Adhesin P1 from Streptococcus mutans

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…IC of HBsAg and MAbs have been reported to stimulate proliferation of immune T lymphocytes more efficiently than did antigen alone (31), and promising therapeutic efficacy of an IC vaccine in the treatment of chronic hepatitis B patients has been reported (125,130). MAbs administered as part of IC have also been demonstrated to influence the humoral immune response against the P1 surface adhesin of the dental pathogen Streptococcus mutans (18,87,99,100). Both the specificity and the isotype of anti-P1 antibodies elicited in immunized mice were altered by the MAbs.…”

Section: Immunization With Immune Complexesmentioning

confidence: 99%