Peptide sequences with strong stimulatory activity for lymphoid cells: implications for vaccine development

• Published in: Vaccine Vol. 11; no. 13; pp. 1310 - 1315
• Main Authors: Russell-Jones, Gregory J., Sullivan, John S., Geczy, Andrew F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.1993; Elsevier
• Subjects: Adjuvants, Immunologic - pharmacology; Amino Acid Sequence; Animals; Antigens, Bacterial - immunology; Antigens, Bacterial - pharmacology; Bacterial Outer Membrane Proteins - immunology; Bacterial Outer Membrane Proteins - pharmacology; Biological and medical sciences; carriers; Cattle; Dogs; Drug Carriers; Epitopes - immunology; Escherichia coli Proteins; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunization; Immunobiology; Lymphocyte Activation - drug effects; Macrophages - drug effects; Macrophages - immunology; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Modulation of the immune response (stimulation, suppression); Molecular Sequence Data; outer-membrane antigen; Peptide Fragments - immunology; Peptide Fragments - pharmacology; Saimiri; subunit vaccines; T-cell epitopes; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Vaccines, Synthetic - immunology; Vaccines, Synthetic - pharmacology; subunit vaccines; carriers; T-cell epitopes; outer-membrane antigen; Human; Membrane protein; Immunostimulation; Synthetic product; Antigenic determinant; Peptides; Escherichia coli; T-Lymphocyte; Bacteria; Vaccine; External membrane; Enterobacteriaceae
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/0264-410X(93)90100-C

Seven peptides derived from the bacterial major outer-membrane protein TraT were synthesized and then tested in lymphoproliferative assays using lymphoid cells from a variety of animals that had been immunized with the native TraT molecule in saline. A hierarchical pattern of responsiveness to the peptides was observed in the four animal species studied and in particular three of the peptides (T2, T4 and T6) showed very strong responses in all species. The ‘universality’ of the TraT-derived peptides was confirmed by studying the responsiveness of lymphoid cells obtained from the peripheral blood of twenty clinically normal human donors. Thus, following a secondary in vitro immunization with TraT-pulsed human peripheral blood mononuclear cells, responsiveness to TraT and to the TraT-derived peptides was observed in the cultures derived from all twenty donors. Taken together, our findings imply that the putative T-cell epitope peptides (T2, T4 and T6) could be employed as carriers in subunit vaccines and thereby help to overcome the unresponsiveness observed in animals and humans as a result of MHC restriction.