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. 1996 Jun;88(2):275–283. doi: 10.1111/j.1365-2567.1996.tb00015.x

Immunogenicity of peptides coupled with multiple T-cell epitopes of a surface protein antigen of Streptococcus mutans.

H Senpuku 1, T Iizima 1, Y Yamaguchi 1, S Nagata 1, Y Ueno 1, M Saito 1, N Hanada 1, T Nisizawa 1
PMCID: PMC1456436  PMID: 8690461

Abstract

A surface protein antigen (PAc) of Streptococcus mutans, in particular the A-region of the molecule, has been noted as a possible target of effective dental caries vaccine. We have previously shown that two peptides of 19 amino acids (residues 361-379, NAKATYEAALKQYEADLAA, and residues 301-319, ANAANEADYQAKLTAYQTE), which correspond to parts of the A-region, contain both T- and B-cell epitopes for the induction of cross-reacting antibodies to the PAc. In this study, for development of an appropriate antigen as a peptide vaccine for use in prophylactic dentistry, we analysed in detail the localization of the T- and B-cell epitopes of PAc(361-379) peptide and the T-cell epitope of PAc(301-319) peptide in B10 congenic mice. In four murine major histocompatibility complex (MHC) haplotypes (H-2f,d,a and k), PAc(361-377) peptide showed T- and B-cell epitopes forming a cluster. It was found that the antibody which was induced by the immunization with the peptide was strongly cross-reactive with recombinant (r)PAc. Meanwhile, PAc(305-318) peptide, recognised by five strains of mice of different MHC haplotypes (H-2f,d,a,k and s), also bore multiple T-cell epitopes. PAc(361-377) peptide coupled to PAc(305-318) significantly elevated cross-reacting antibody levels compared to immunization with PAc(361-377) only in four H-2 haplotypes. Moreover, a peptide with PAc(305-318) coupled to the N-terminal region of PAc(361-377) produced significant cross-reacting antibody against rPAc, even in B10.S mice which had not responded to immunization with PAc(361-379) peptide. Therefore, it was suggested that coupling among the peptides forming a cluster might be effective in increasing immunogenicity. These results may provide us with a useful strategy for the design of peptide-based vaccines for S. mutans in the future.

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Selected References

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  1. Ahlers J. D., Pendleton C. D., Dunlop N., Minassian A., Nara P. L., Berzofsky J. A. Construction of an HIV-1 peptide vaccine containing a multideterminant helper peptide linked to a V3 loop peptide 18 inducing strong neutralizing antibody responses in mice of multiple MHC haplotypes after two immunizations. J Immunol. 1993 Jun 15;150(12):5647–5665. [PubMed] [Google Scholar]
  2. Berzofsky J. A., Pendleton C. D., Clerici M., Ahlers J., Lucey D. R., Putney S. D., Shearer G. M. Construction of peptides encompassing multideterminant clusters of human immunodeficiency virus envelope to induce in vitro T cell responses in mice and humans of multiple MHC types. J Clin Invest. 1991 Sep;88(3):876–884. doi: 10.1172/JCI115389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brady L. J., Piacentini D. A., Crowley P. J., Oyston P. C., Bleiweis A. S. Differentiation of salivary agglutinin-mediated adherence and aggregation of mutans streptococci by use of monoclonal antibodies against the major surface adhesin P1. Infect Immun. 1992 Mar;60(3):1008–1017. doi: 10.1128/iai.60.3.1008-1017.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crowley P. J., Brady L. J., Piacentini D. A., Bleiweis A. S. Identification of a salivary agglutinin-binding domain within cell surface adhesin P1 of Streptococcus mutans. Infect Immun. 1993 Apr;61(4):1547–1552. doi: 10.1128/iai.61.4.1547-1552.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Demuth D. R., Lammey M. S., Huck M., Lally E. T., Malamud D. Comparison of Streptococcus mutans and Streptococcus sanguis receptors for human salivary agglutinin. Microb Pathog. 1990 Sep;9(3):199–211. doi: 10.1016/0882-4010(90)90022-i. [DOI] [PubMed] [Google Scholar]
  6. Etlinger H. M. Carrier sequence selection--one key to successful vaccines. Immunol Today. 1992 Feb;13(2):52–55. doi: 10.1016/0167-5699(92)90134-S. [DOI] [PubMed] [Google Scholar]
  7. Forester H., Hunter N., Knox K. W. Characteristics of a high molecular weight extracellular protein of Streptococcus mutans. J Gen Microbiol. 1983 Sep;129(9):2779–2788. doi: 10.1099/00221287-129-9-2779. [DOI] [PubMed] [Google Scholar]
  8. Hajishengallis G., Koga T., Russell M. W. Affinity and specificity of the interactions between Streptococcus mutans antigen I/II and salivary components. J Dent Res. 1994 Sep;73(9):1493–1502. doi: 10.1177/00220345940730090301. [DOI] [PubMed] [Google Scholar]
  9. Hale P. M., Cease K. B., Houghten R. A., Ouyang C., Putney S., Javaherian K., Margalit H., Cornette J. L., Spouge J. L., DeLisi C. T cell multideterminant regions in the human immunodeficiency virus envelope: toward overcoming the problem of major histocompatibility complex restriction. Int Immunol. 1989;1(4):409–415. doi: 10.1093/intimm/1.4.409. [DOI] [PubMed] [Google Scholar]
  10. Hamada S., Slade H. D. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev. 1980 Jun;44(2):331–384. doi: 10.1128/mr.44.2.331-384.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hammer J., Valsasnini P., Tolba K., Bolin D., Higelin J., Takacs B., Sinigaglia F. Promiscuous and allele-specific anchors in HLA-DR-binding peptides. Cell. 1993 Jul 16;74(1):197–203. doi: 10.1016/0092-8674(93)90306-b. [DOI] [PubMed] [Google Scholar]
  12. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  13. Kelly C. G., Todryk S., Kendal H. L., Munro G. H., Lehner T. T-cell, adhesion, and B-cell epitopes of the cell surface Streptococcus mutans protein antigen I/II. Infect Immun. 1995 Sep;63(9):3649–3658. doi: 10.1128/iai.63.9.3649-3658.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koga T., Okahashi N., Takahashi I., Kanamoto T., Asakawa H., Iwaki M. Surface hydrophobicity, adherence, and aggregation of cell surface protein antigen mutants of Streptococcus mutans serotype c. Infect Immun. 1990 Feb;58(2):289–296. doi: 10.1128/iai.58.2.289-296.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lee S. F., Progulske-Fox A., Erdos G. W., Piacentini D. A., Ayakawa G. Y., Crowley P. J., Bleiweis A. S. Construction and characterization of isogenic mutants of Streptococcus mutans deficient in major surface protein antigen P1 (I/II). Infect Immun. 1989 Nov;57(11):3306–3313. doi: 10.1128/iai.57.11.3306-3313.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lehner T., Caldwell J., Smith R. Local passive immunization by monoclonal antibodies against streptococcal antigen I/II in the prevention of dental caries. Infect Immun. 1985 Dec;50(3):796–799. doi: 10.1128/iai.50.3.796-799.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ma J. K., Hunjan M., Smith R., Lehner T. Specificity of monoclonal antibodies in local passive immunization against Streptococcus mutans. Clin Exp Immunol. 1989 Sep;77(3):331–337. [PMC free article] [PubMed] [Google Scholar]
  18. Ma J. K., Smith R., Lehner T. Use of monoclonal antibodies in local passive immunization to prevent colonization of human teeth by Streptococcus mutans. Infect Immun. 1987 May;55(5):1274–1278. doi: 10.1128/iai.55.5.1274-1278.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Matsushita S., Takahashi K., Motoki M., Komoriya K., Ikagawa S., Nishimura Y. Allele specificity of structural requirement for peptides bound to HLA-DRB1*0405 and -DRB1*0406 complexes: implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome. J Exp Med. 1994 Sep 1;180(3):873–883. doi: 10.1084/jem.180.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moisset A., Schatz N., Lepoivre Y., Amadio S., Wachsmann D., Schöller M., Klein J. P. Conservation of salivary glycoprotein-interacting and human immunoglobulin G-cross-reactive domains of antigen I/II in oral streptococci. Infect Immun. 1994 Jan;62(1):184–193. doi: 10.1128/iai.62.1.184-193.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nakai M., Okahashi N., Ohta H., Koga T. Saliva-binding region of Streptococcus mutans surface protein antigen. Infect Immun. 1993 Oct;61(10):4344–4349. doi: 10.1128/iai.61.10.4344-4349.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ogasawara K., Naruse H., Itoh Y., Gotohda T., Arikawa J., Kida H., Good R. A., Onoé K. A strategy for making synthetic peptide vaccines. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8995–8999. doi: 10.1073/pnas.89.19.8995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Okahashi N., Sasakawa C., Yoshikawa M., Hamada S., Koga T. Cloning of a surface protein antigen gene from serotype c Streptococcus mutans. Mol Microbiol. 1989 Feb;3(2):221–228. doi: 10.1111/j.1365-2958.1989.tb01811.x. [DOI] [PubMed] [Google Scholar]
  24. Okahashi N., Sasakawa C., Yoshikawa M., Hamada S., Koga T. Molecular characterization of a surface protein antigen gene from serotype c Streptococcus mutans, implicated in dental caries. Mol Microbiol. 1989 May;3(5):673–678. doi: 10.1111/j.1365-2958.1989.tb00215.x. [DOI] [PubMed] [Google Scholar]
  25. Okahashi N., Takahashi I., Nakai M., Senpuku H., Nisizawa T., Koga T. Identification of antigenic epitopes in an alanine-rich repeating region of a surface protein antigen of Streptococcus mutants. Infect Immun. 1993 Apr;61(4):1301–1306. doi: 10.1128/iai.61.4.1301-1306.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Russell M. W., Bergmeier L. A., Zanders E. D., Lehner T. Protein antigens of Streptococcus mutans: purification and properties of a double antigen and its protease-resistant component. Infect Immun. 1980 May;28(2):486–493. doi: 10.1128/iai.28.2.486-493.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Russell M. W., Lehner T. Characterisation of antigens extracted from cells and culture fluids of Streptococcus mutans serotype c. Arch Oral Biol. 1978;23(1):7–15. doi: 10.1016/0003-9969(78)90047-x. [DOI] [PubMed] [Google Scholar]
  28. Russell M. W., Mansson-Rahemtulla B. Interaction between surface protein antigens of Streptococcus mutans and human salivary components. Oral Microbiol Immunol. 1989 Jun;4(2):106–111. doi: 10.1111/j.1399-302x.1989.tb00107.x. [DOI] [PubMed] [Google Scholar]
  29. Russell R. R., Beighton D., Cohen B. Immunisation of monkeys (Macaca fascicularis) with antigens purified from Streptococcus mutans. Br Dent J. 1982 Feb 2;152(3):81–84. doi: 10.1038/sj.bdj.4804751. [DOI] [PubMed] [Google Scholar]
  30. Russell R. R. Wall-associated protein antigens of Streptococcus mutans. J Gen Microbiol. 1979 Sep;114(1):109–115. doi: 10.1099/00221287-114-1-109. [DOI] [PubMed] [Google Scholar]
  31. Sarobe P., Lasarte J. J., Larrea E., Golvano J. J., Prieto I., Gullón A., Prieto J., Borrás-Cuesta F. Enhancement of peptide immunogenicity by insertion of a cathepsin B cleavage site between determinants recognized by B and T cells. Res Immunol. 1993 May;144(4):257–262. doi: 10.1016/0923-2494(93)80102-5. [DOI] [PubMed] [Google Scholar]
  32. Schaeffer E. B., Sette A., Johnson D. L., Bekoff M. C., Smith J. A., Grey H. M., Buus S. Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4649–4653. doi: 10.1073/pnas.86.12.4649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Senpuku H., Miyauchi T., Hanada N., Nisizawa T. An antigenic peptide inducing cross-reacting antibodies inhibiting the interaction of Streptococcus mutans PAc with human salivary components. Infect Immun. 1995 Dec;63(12):4695–4703. doi: 10.1128/iai.63.12.4695-4703.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Senpuku H., Nakai M., Koga T., Hanada N., Nisizawa T. Identification of a repeated epitope recognized by human serum antibodies in a surface protein antigen of Streptococcus mutans. Oral Microbiol Immunol. 1996 Apr;11(2):121–128. doi: 10.1111/j.1399-302x.1996.tb00346.x. [DOI] [PubMed] [Google Scholar]
  35. Shaw D. M., Stanley C. M., Partidos C. D., Steward M. W. Influence of the T-helper epitope on the titre and affinity of antibodies to B-cell epitopes after co-immunization. Mol Immunol. 1993 Aug;30(11):961–968. doi: 10.1016/0161-5890(93)90121-q. [DOI] [PubMed] [Google Scholar]
  36. Stern L. J., Brown J. H., Jardetzky T. S., Gorga J. C., Urban R. G., Strominger J. L., Wiley D. C. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature. 1994 Mar 17;368(6468):215–221. doi: 10.1038/368215a0. [DOI] [PubMed] [Google Scholar]
  37. Takahashi I., Matsushita K., Nisizawa T., Okahashi N., Russell M. W., Suzuki Y., Munekata E., Koga T. Genetic control of immune responses in mice to synthetic peptides of a Streptococcus mutans surface protein antigen. Infect Immun. 1992 Feb;60(2):623–629. doi: 10.1128/iai.60.2.623-629.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Takahashi I., Okahashi N., Matsushita K., Tokuda M., Kanamoto T., Munekata E., Russell M. W., Koga T. Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen. J Immunol. 1991 Jan 1;146(1):332–336. [PubMed] [Google Scholar]
  39. Zegers N. D., van Holten C., Claasen E., Boersma W. J. Peptide-induced memory (IgG) response, cross-reactive with native proteins, requires covalent linkage of a specific B cell epitope with a T cell epitope. Eur J Immunol. 1993 Mar;23(3):630–634. doi: 10.1002/eji.1830230308. [DOI] [PubMed] [Google Scholar]

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