| Project/Area Number |
12557158
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
SENPUKU Hidenobu National Institute of Infectious Diseases, Department of Bacteriology, Head, Oral infectious diseases, 細菌第一部, 室長 (20250186)
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| Co-Investigator(Kenkyū-buntansha) |
ASANO Toshihiko National Institute of Infectious Diseases, Department of Experimental Animal Research, Head, 動物管理室, 室長 (60100062)
MURATA Takatoshi Kyushu Dental College, Department of Oral Science, Assistant Professor, 口腔科学, 助手 (10313529)
HANADA Nobuhiro National Institute of Pubric Health, Department of Oral Health, Director, 口腔保健部, 部長 (70180916)
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| Project Period (FY) |
2000 – 2002
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| Keywords | PAc(361-386) peptide / Streptococcus mutans / NOD-scid mouse / Monoclonal antibody / 3DS / PMTC / DRB1 / Epitope |
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| Research Abstract |
Alanine-rich repeating region (A-region) in surface protein antigen (Pac) of Streptococcus mutans has been given much attention as an antigenic component for dental caries vaccines. The Pac (residue 361-386) peptide in A-region possesses a multiple binding motif (L--V-K-A) to various HLA-DR molecules and the B-cell core epitope (Y---L--Y) recognizing by the inhibiting antibody to S. mutans. In this study, we investigated whether Pac (361-386) peptide was effective antigen for induction of the inhibiting antibody in human, and what correlate with the antibody induction in saliva. Stimulated saliva samples were collected from 151 healthy human subjects (age : 36.6±12.6). NOD-scid mice grafted with human peripheral blood mononuclear cells (PBMC)were used to examine immunogenicity of Pac (361-386) peptide. Hu- IgA and IgG antibody titers to Pac (361-386) peptide in the human saliva and sera from the grafted mice were analyzed by enzyme-linked immuno sorbent assay. Anti-Pac(361-386) peptide IgA antibody titer (a) in human saliva decreased significantly in age-dependent mannaer. MS and mS/ tS ratio were lower in high antibody group (3<a) than no antibody (0.1>a) and moderate group (3≧a>1). Allel DRB1^*1501 and DRB1^*0406 were significantly correlated with high induction of the antibodies and also tended to reduce Lactobacilli and S. mutans. Moreover, the peptide immunogenicities were confirmed in the grafted NOD-scid mice expressing various DRB1 genotypes. The monoclonal antibody induced by the peptide immunization (SH2, KH5) inhibited S. mutans colonization on the tooth surfaces in rats. Therefore, the Pac(361-386) peptide has strong immunogenicity and induce the inhibiting antibody in human oral cavity, and the induction are regulated by aging, HLA-DRB1 genotype and cytokine. These results may be helpful in removing system of oral biofilm using Dental Drug delivary system(3DS) with the human monoclonal antibody to prevent dental diseases.
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