Identification of T- and B-cell epitopes in synthetic peptides derived from a Streptococcus mutans protein and characterization of their antigenicity and immunogenicity.

Natural immunity to synthetic peptides (SP) derived from the sequences of a 3800 Mr Streptococcus mutans antigen was found in human subjects. Significant serum IgG antibodies were detected both to the native streptococcal antigen and to the SP17, containing essentially residues 1-15. A series of short peptides with deletions at the amino- and carboxy-termini were then tested to identify the B-cell epitopes. Residues 8-13 and 1-6 bound significant serum IgG antibodies but only the former consistently inhibited human antibodies, suggesting that residues 8-13 constitute a major B-cell epitope. The human CD4 subset of T-cells was then examined and this showed a significant uptake of [3H]-thymidine when stimulated with both the native streptococcal antigen and the SP17. The series of short peptides was then used to stimulate CD4 cells, in order to determine the T-cell epitope. The synthetic peptide with residues 6-15 was the shortest peptide that stimulated significant [3H]-thymidine uptake and this peptide was designated as a T-cell epitope. The immunogenicity and antigenicity of SP17 was also investigated in macaques. Immunization of monkeys with the free SP17 failed to elicit serum antibodies or T-cell responses. However, immunization with SP17 linked to tetanus toxoid as a carrier elicited serum antibodies and proliferative responses of lymphocytes, not only to the synthetic peptide but also to the native streptococcal antigen. As in the human studies a B-cell epitope was found in residues 8-13, whereas an overlapping T-cell epitope was located in residues 7-15.(ABSTRACT TRUNCATED AT 250 WORDS)