Role of peptide antigen for induction of inhibitory antibodies to Streptococcus mutans in human oral cavity
Y. TSUHA
Department of Comprehensive Oral Health Care, Graduate School, Tokyo Medical and Dental University,
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorN. HANADA
Department of Oral Health, National Institute of Public Health,
Search for more papers by this authorT. ABEI
Division of Experimental Animal Research, National Institute of Infectious Diseases
Search for more papers by this authorS. YAMAGUCHI
Division of Experimental Animal Research, National Institute of Infectious Diseases
Search for more papers by this authorM. A. SALAM
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorR. NAKAO
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorH. TAKEUCHI
Department of Oral Health, National Institute of Public Health,
Search for more papers by this authorN. KUROSAKI
Department of Comprehensive Oral Health Care, Graduate School, Tokyo Medical and Dental University,
Search for more papers by this authorCorresponding Author
H. SENPUKU
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Hidenobu Senpuku, Department of Bacteriology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162–8640, Japan. E-mail: [email protected]Search for more papers by this authorY. TSUHA
Department of Comprehensive Oral Health Care, Graduate School, Tokyo Medical and Dental University,
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorN. HANADA
Department of Oral Health, National Institute of Public Health,
Search for more papers by this authorT. ABEI
Division of Experimental Animal Research, National Institute of Infectious Diseases
Search for more papers by this authorS. YAMAGUCHI
Division of Experimental Animal Research, National Institute of Infectious Diseases
Search for more papers by this authorM. A. SALAM
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorR. NAKAO
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Search for more papers by this authorH. TAKEUCHI
Department of Oral Health, National Institute of Public Health,
Search for more papers by this authorN. KUROSAKI
Department of Comprehensive Oral Health Care, Graduate School, Tokyo Medical and Dental University,
Search for more papers by this authorCorresponding Author
H. SENPUKU
Department of Bacteriology, National Institute of Infectious Diseases, Tokyo, Japan
Hidenobu Senpuku, Department of Bacteriology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162–8640, Japan. E-mail: [email protected]Search for more papers by this authorSUMMARY
The alanine-rich repeating region (A-region) in the surface protein antigen (PAc) of Streptococcus mutans has received much attention as an antigenic component for vaccines against dental caries. The PAc (residue 361–386) peptide in the A-region possesses a multiple binding motif (L- -V-K- -A) to various HLA-DR molecules and a B-cell core epitope (- Y- - -L- -Y- - - -) that recognizes the inhibiting antibody to S. mutans. In the present study, we investigated the immunogenicity of the PAc (361–386) peptide in humans and regulators of induction of the anti-PAc (361–386) peptide IgA antibody (aPPA) in saliva. The PAc (361–386) peptide was confirmed as an ideal peptide antigen for induction of the inhibiting antibody to S. mutans in 151 healthy human subjects (36·6 ± 12·6 years old) by quantitative analyses of oral bacteria and ELISA, as the aPPA titre in human saliva decreased significantly in an age-dependent manner. Homozygous DRB1*0405 and 1502, and heterozygous DRB1*0405/1502 showed a negative association with production of aPPA and tended to reduce the number of total streptococci in saliva. In contrast, the DRB1*1501 allele was significantly correlated with a high level of induction of the antibodies, and also tended to reduce lactobacilli and mutans streptococci. Further, peptide immunogenicity was confirmed in NOD-SCID mice grafted with human peripheral blood mononuclear cells. Our results indicate that the interplay between regulators such as age, DRB1 genotype, cytokines, and peptide immunogenicity may provide a potential means for developing a vaccine useful for the prevention of dental caries as well as their diagnosis.
REFERENCES
- 1 Hamada S, Slade HD. Biology, immunology, and cariogenicity of Streptococcus mutans. Microbiol Rev 1980; 44: 331–84.
- 2 Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev 1986; 50: 353–80.
- 3 Granath L, Cleaton-Jones P, Fatti LP, Grossman ES. Prevalence of dental caries in 4- to 5-year-old children partly explained by presence of salivary mutans streptococci. J Clin Microbiol 1993; 31: 66–70.
- 4 Kristoffersson K, Axelsson P, Birkhed D, Bratthall D. Caries prevalence, salivary Streptococcus mutans and dietary scores in 13-year-old Swedish schoolchildren. Community Dent Oral Epidemiol 1986; 14: 202–5.
- 5 Thibodeau EA, O'Sullivan DM. Salivary mutans streptococci and caries development in the primary and mixed dentitions of children. Community Dent Oral Epidemiol 1999; 27: 406–12.
- 6 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; 3: 221–8.
- 7 Russell MW, Lehner T. Characterisation of antigens extracted from cells and culture fluids of Streptococcus mutans serotype c. Arch Oral Biol 1978; 23: 7–15.
- 8 Forestor H, Hunter N, Knox KW. Characteristics of a high molecular weight extracellular protein of Streptococcus mutans. J General Microbiol 1983; 129: 2779–88.
- 9 Russell RR. Wall-associated protein antigens of Streptococcus mutans. J General Microbiol 1979; 114: 109–15.
- 10 Demuth DR, Lammey MS, Huck M, Lally ET, Malamud D. Comparison of Streptococcus mutans and Streptococcus sanguis receptors for human salivary agglutinin. Microb Pathog 1990; 9: 199–211.
- 11 Russell MW, Masson-Rahemtulla B. Interaction between surface protein antigen of Streptococcus mutans and human salivary components. Oral Microbiol Immunol 1989; 4: 106–11.
- 12 Senpuku H, Kato H, Todoroki M, Hanada N, Nisizawa T. Interaction of lysozyme with a surface protein antigen of Streptococcus mutans. FEMS Microbiol Lett 1996; 39: 195–201.
- 13 Brady LJ, Piacentini DA, Crowley PJ, Oyston PC, Bleiweis AS. Differentiation of salivary agglutinin-mediated adherence and aggregation of mutans streptococci by use of monoclonal antibodies against the major surface adhesion P1. Infect Immun 1992; 60: 1008–17.
- 14 Nakai M, Okahashi N, Ohta N, Koga T. Saliva-binding region of Streptococcus mutans surface protein antigen. Infect Immun 1993; 61: 4344–9.
- 15 , YuH, Nakano Y, Yamashita Y, Oho T, Koga T. Effects of antibodies against cell surface protein antigen PAc-glucosyltransferase fusion proteins on glucan synthesis and cell adhesion of Streptococcus mutans. Infect Immun 1997; 65: 2292–8.
- 16 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; 11: 121–8.
- 17 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; 63: 4695–703.
- 18 Senpuku H, Matin K, Salam MA, Kurauchi I, Sakurai S, Kawashima M, Murata T, Hanada N. Inhibitory effects of monoclonal antibodies against a surface protein antigen in real-time adherence in vitro and recolonization in vivo of Streptococcus mutans. Scand. J Immunol 2001; 54: 109–16.
- 19 Senpuku H, Iizima T, Yamaguchi Y, Nagata S, Ueno Y, Saito M, Hanada N, Nisizawa T. Immunogenicity of peptides coupled with multiple T-cell epitopes of a surface protein antigen of Streptococcus mutans. Immunology 1996; 88: 275–83.
- 20 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 mutans. Infect Immun 1993; 61: 1301–6.
- 21 Senpuku H, Kato H, Takeuchi H, Noda A, Nisizawa T. Identification of core B cell epitope in the synthetic peptide inducing cross-inhibiting antibodies to a surface protein antigen of Streptococcus mutans. Immunol Invest 1997; 26: 531–48.
- 22 Nomura Y, Eto A, Hanada N, Senpuku H. Identification of the peptide motifs that interact with HLA-DR8 (DRB1*0802) in Streptococcus mutans proteins. Oral Microbiol Immunol 2002; 17: 209–14.
- 23 Senpuku H, Yanagi K, Nisizawa T. Identification of Streptococcus mutans PAc peptide motif binding with humans MHC class II molecules (DRB1*0802, *1101, *1401 and *1405). Immunology 1998; 95: 322–30.
- 24 Brandtzarg P. Salivary immunoglobulins. In: J Tenovuo, ed. Human Saliva: Clinical Chemistry and Microbiology, Vol. II. Buca Raton FL: CRC Press, 1989: 1–54.
- 25
Kiyono H,
Ogra PL,
McGhee JR.
Mucosal Vaccines. SanDiego: Academic Press, 1996.
10.1016/B978-012410580-5/50007-8 Google Scholar
- 26 Zhang P, Jespersgaard C, Lamperty-Mallory L, Katz J, Huang Y, Hajishengallis G, Michalek SM. Enhanced immunogenicity of a genetic chimeric protein consisting of two virulence antigens of Streptococcus mutans and protection against infection. Infect Immun 2002; 70: 6779–87.
- 27 Lehner T, Caldwell J, Smith R. Local passive immunization by monoclonal antibodies against streptococcal antigen I/II in the prevention of dental carries. Infect Immun 1985; 50: 796–9.
- 28 Ma JK, Hikmat BY, Wycoff K, Vine ND, Chargelegue DYuL, Hein MB, Lehner T. Characterization of a recombinant plant monoclonal secretary antibody and preventive immunotheraphy in humans. Nat Med 1998; 4: 601–5.
- 29 Takeuchi H, Fukushima K, Senpuku H et al. Clinical study of mutans streptococci using 3DS and monoclonal antibodies. Jpn J Infect Dis 2001; 54: 34–6.
- 30 Bolton RW, Hlava GL. Evaluation of salivary IgA antibodies to cariogenic microorganisms in children correlation with dental caries activity. J Dent Res 1982; 61: 1225–8.
- 31 Challacombe SJ, Lehner T. Serum and salivary antibodies to cariogenic bacteria in man. J Dent Res 1976; 55: C139–48.
- 32 Lehtonen OP, Grahn EM, Stahlberg TH, Laitinen LA. Amount and avidity of salivary and serum antibodies against Streptococcus mutans in two groups of human subjects with different dental caries susceptibility. Infect Immun 1984; 43: 308–13.
- 33 Gonwa TA, Peterlin BM, Stobo JD. Human-Ir genes: structure and function. Adv Immunol 1983; 34: 71–96.
- 34 Roitt I, Brostoff J, Male D. Immunology, 5th edn. London: Mosby International, 1998.
- 35 Wallengren ML, Ericson D, Hamberg K, Johnson. U. HLA-DR4 and salivary immunoglobulin A reactions to oral streptococci. Oral Microbiol Immunol 2001; 16: 45–53.
- 36 Greiner DL, Shultz LD, Yates J et al. Improved engraftment of human spleen cells in NOD/LtSz-scid/scid mice as compared with C.B-17-scid/scid mice. Am J Pathol 1995; 146: 888–902.
- 37 Hesselton RM, Greiner DL, Mordes JP, Rajan TV, Sullivan JL, Shultz LD. High levels of human peripheral blood mononuclear cell engraftment and enhanced susceptibility to human immunodeficiency virus type I infection in NOD/LtSz-scid/scid mice. J Infect Dis 1995; 172: 974–82.
- 38 Shultz LD, Schweitzer PA, Christianson SW et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol 1995; 154: 180–91.
- 39 World Health Organization Oral Health Surveys. Basic Methods. Geneva: WHO, 1986.
- 40 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; 3: 673–8.
- 41 Ellner PD, Stoessel CJ, Drakeford E, Vasi F. A new culture medium for medical bacteriology. Am J Clin Pathol 1966; 45: 502–4.
- 42 Gold OG, Jordan HV, Van Houte J. A selective medium for Streptococcus mutans. Arch Oral Biol 1973; 18: 1357–64.
- 43 Ida H, Hanada N, Sato T, Yoshikawa E. Establishment of selective medium for mutans streptococci and detection system. In: N Hanada, ed. Clinical biology of the mutans streptococci. Tokyo: Quintessence Inc, 2003: 82–9 (In Japanese).
- 44 Suzuki T, Tagami J, Hanada N. Role of F1F0-ATPase in the growth of Streptococcus mutans GS5. J Appl Microbiol 2000; 88: 555–62.
- 45 Senpuku H, Asano T, Matin K et al. Effects of human IL-18 and IL-12 treatment on human lymphocyte engraftment in NOD-scid mouse. Immunology 2002; 107: 232–42.
- 46 Paul WE. Interleukin-4: a prototypic immunoregulatory lymphokine. Blood 1991; 77: 1859–70.
- 47 Paul WE, Seder RA. Lymphocyte responses and cytokines. Cell 1994; 76: 241–51.
- 48 Kopf M, Le Gros G, Bachmann M, Lamers MC, Bluethmann H, Kohler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 1993; 362: 245–8.
- 49 Taubman MA, Holmberg CJ, Smith DJ. Immunization of rats with synthetic peptide constructs from the glucan-binding or catalytic region of mutans streptococcal glucosyltransferase protects against dental caries. Infect Immun 1995; 63: 3088–93.
- 50 Smith DJ, King WF, Barnes LA, Peacoc Zk Taubman MA. Immunogenicity and protective immunity induced by synthetic peptides associated with putative immunodominant regions of Streptococcus mutans glucan-binding protein B. Infect Immun 2003; 71: 1179–84.
- 51 Takahashi I, Okahashi N, Matsushita K, Tokuda M, Kanamoto T, Munekata E, Russell MW, Koga T. Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen. J Immunol 1991; 146: 332–6.
- 52 Wallengren ML, Ericson D, Forsberg B, Johnson U. Human leukocyte antigens in relation to colonization by mutans streptococci in the oral cavity. Oral Microbiol Immunol 1991; 6: 292–4.
- 53 Kurihara Y, Naito T, Obayashi K, Hirasawa M, Kurihara Y, Moriwaki K. Caries susceptibility in inbred mouse strains and inheritance patterns in F1 and backcross (N2) progeny from strains with high and low caries susceptibility. Caries Res 1991; 25: 341–6.
- 54 Lehner T, Lamb JR, Welsh KL, Batchelor RJ. Association between HLA-DR antigens and helper cell activity in the control of dental caries. Nature 1981; 292: 770–2.
- 55 Niiyama T, Kojima H, Mizuno K et al. Genetic control of the immune responsiveness to Streptococcus mutans by the major histocompatibility complex of the rat (RT1). Infect Immun 1987; 55: 3137–41.
- 56 Acton RT, Dasanayake AP, Harrison RA, Li Y, Roseman JM, Go RC, Wiener H, Caufield PW. Associations of MHC genes with levels of caries-inducing organisms and caries severity in African-American women. Hum Immunol 1999; 60: 984–9.
- 57 Ozawa Y, Chiba J, Sakamoto S. HLA class II alleles and salivary numbers of mutans streptococci and lactobacilli among young adults in Japan. Oral Microbiol Immunol 2001; 16: 353–7.
- 58 Yoshitake S, Okada M, Kimura A, Sasazuki T. Contribution of major histocompatibility complex genes to susceptibility and resistance in Helicobacter pylori related diseases. Eur. J Gastroenterol Hepatol 1999; 11: 875–80.
- 59 Kotb M, Norrby-Teglund A, McGeer A et al. An. immunogenetic and molecular basis for differences in outcomes of invasive group A streptococcal infections. Nat Med 2002; 8: 1398–404.
- 60 Hunt RJ, Drake CW, Beck JD. Streptococcus mutans, Lactobacillus and caries experience in older adults. Spec Cre Dentist 1992; 12: 149–52.
- 61 Costerton JW, Cheng KJ, Geesy GG, Ladd TI, Nichel JD, Dugupta M, Marie JJ. Bacterial biofilms in nature and diseases. Annu Rev Microbiol 1987; 41: 435–64.
- 62 Saito M, Otake S, Ohmura M et al. Protective immunity to Streptococcus mutans induced by nasal vaccination with surface protein antigen and mutant cholera toxin adjuvant. J Infect Dis 2001; 183: 823–6.