Role of peptide antigen for induction of inhibitory antibodies to Streptococcus mutans in human oral cavity.
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.
Tsuha
Y
Y
Department of Comprehensive Oral Health Care, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Hanada
N
N
Asano
T
T
Abei
T
T
Yamaguchi
S
S
Salam
M A
MA
Nakao
R
R
Takeuchi
H
H
Kurosaki
N
N
Senpuku
H
H
D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009055:Mouth / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D012463:Saliva / Q000276:immunology; D013295:Streptococcus mutans / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; C055764:S-layer proteins