Identification of Streptococcus mutans PAc peptide motif binding with human MHC class II molecules (DRB1*0802, *1101, *1401 and *1405).
A surface protein antigen (PAc) of Streptococcus mutans, in particular the A-region of this PAc molecule, has been noted as a possible target in research for an effective dental caries vaccine. To identify the antigenic peptide binding to major histocompatibility complex (MHC) class II (HLA-DR) molecules in the A-region, we prepared a panel of overlapping synthetic peptides in the second unit of the A-region, and established that a simple enzyme-linked immunosorbent assay (ELISA) binding assay could be achieved by incubating the DR-crude. Binding to DR molecules of these peptides from nine donors was investigated by using the ELISA binding assay. It was revealed that the PAc(316-334) peptide bound more strongly to the HLA-DR molecule in seven out of nine subjects. In particular, DR8 (DRB1*0802), DR5 (DRB1*1101) and DR6 (DRB1*1402 and *1405), which bound strongly to PAc(316-334) peptide, were identified. Moreover, we synthesized glycine-substituted peptide analogues of the peptide and examined the binding motif of the binding region. As a result, the multiple binding motif in DR8, DR5 and DR6 was found in L-RV-K-A. It is suggested that a peptide vaccine for dental caries that is more effective for humans, with fewer adverse side-effects, could be designed by combining the multiple binding motif with the B-cell epitope to produce only the inhibiting antibody against dental caries. The peptide could therefore be useful for peptide vaccine development in the general human population.
Senpuku
H
H
Department of Oral Science, National Institute of Infectious Diseases, Tokyo, Japan.
Yanagi
K
K
Nisizawa
T
T
D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D008562:Membrane Glycoproteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D013291:Streptococcus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; C055764:S-layer proteins; D014614:Vaccines, Synthetic