Induction of CD4(+) and CD8(+) Bordetella pertussis toxin subunit S1 specific T cells by immunization with synthetic peptides.
In this study two synthetic peptides from the Bordetella pertussis toxin subunit S1 were conjugated to human anti-idiotypic antibodies and used as an immunogen in cancer patients to induce immunity. The aims of the present report are to explain why no carrier or adjuvant effect of the conjugated pertussis peptides could be established regarding induction of responses against the anti-idiotype and to explore the type and quality of induced anti-pertussis immune responses. The lack of carrier and adjuvant effect of the peptides might be related to the fact that the anti-idiotypic antibodies by themselves include helper epitopes and that none of the patients had a detectable T cell response against any of the selected peptides before immunization, which might be a requirement for an adjuvant effect. However, three of four immunized patients mounted a humoral as well as cellular response against the pertussis peptides used. The induced T cell immunity was restricted to one of the two peptides in responding patients. Established T cell lines and MHC blocking studies indicated that the T cell epitopes of the two peptides had a different MHC restriction. The type of T cell response induced seemed to govern the humoral response. The only durable antibody response was accompanied by the presence of a CD4(+) T cell response against the same peptide. Immunization with an anti-idiotype conjugated to synthetic peptides might thus induce both a B and a T cell response against the peptides and the type of induced T cells (CD4 or CD8) governs the quality of the humoral response. Moreover, the possibility of boosting or inducing a response against the antigen from which the peptide sequences were deduced also seemed feasible.
Fagerberg
J
J
Department of Oncology (Radiumhemmet), Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden.
Askelöf
P
P
Wigzell
H
H
Mellstedt
H
H
D000230:Adenocarcinoma / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology* / Q000627:therapeutic use; D001886:Bordetella pertussis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D007114:Immunization; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D006680:HLA Antigens; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin