Non-responsiveness to a foot-and-mouth disease virus peptide overcome by addition of foreign helper T-cell determinants.
Study of the immune response to synthetic antigens has shown that uncoupled peptides can realize their potential as vaccines only if they contain domains that react with helper T-cell receptors and Ia antigens in addition to antibody binding sites. Here we consider whether genetically restricted non-responsiveness to an uncoupled peptide could be overcome by synthesizing a peptide with an additional helper T-cell epitope from a different protein. We demonstrate that H-2d mice, which are non-responders to the 141-160 VP1 peptide of foot-and-mouth disease virus (FMDV), can be converted into responders by immunization with peptides containing the FMDV sequence with defined 'foreign' helper T-cell determinants from ovalbumin or sperm whale myoglobin. Furthermore, the virus-neutralizing activity of the antibody raised against peptide was dependent on the determinant used. Thus, FMDV peptides with the added sequences 323-339 from ovalbumin and 132-148 from sperm-whale myoglobin elicited a high degree of neutralizing activity in B10.D2 mice. The sera from mice which received the peptide with the added sequence 105-121 from sperm whale myoglobin did not neutralize the virus, although they had high levels of anti-141-160 FMDV peptide activity. Our data indicate that the T-cell help given by the 'foreign' epitopes is B-cell clone specific. These results are likely to have important implications for the design of peptide vaccines.
D000818:Animals; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology*; D005537:Aphthovirus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010455:Peptides / Q000276:immunology*; D013045:Species Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D010455:Peptides