International Immunology, Vol. 15, No. 6, pp. 691-699,
June 2003
© 2003 Japanese Society for Immunology
Engineering Th determinants for efficient priming of humoral and cytotoxic T cell responses
1 Universidad de Navarra, Division de Hepatología y Terapia Génica, Facultad de Medicina. Irunlarrea 1, 31008 Pamplona, Spain
Correspondence to: F. Borrás-Cuesta; E-mail: fborras{at}unav.es
Transmitting editor: T. Watanabe
To engineer Th determinants (THd) to prime help for humoral or cytotoxic T cell responses, we modified ovalbumin [OVA323–337] and myoglobin [MYO106–118] eliciting Th1 and Th0 cytokine profiles respectively. Residues along the sequence of both THd were replaced with amino acids representative of different families. Replacements at positions P–1 and P5 pointing to the TCR in both THd afforded higher levels of IFN-
and IL-4 production. Peptides eliciting different proportions of IFN- and IL-4 were co-immunized with a peptide hapten or a T cytotoxic determinant (TCd) respectively. OVA323–337- and MYO106–118-derived peptides afforded the best THd for the induction of cytotoxic T lymphocyte (CTL) and anti-hapten antibodies respectively. IFN- and IL-4, primed by MYO106–118-derived peptides, correlated significantly with antibody production against the hapten (P < 0.05 for IFN- and P < 0.05 for IL-4). Interestingly, two peptides derived from OVA323–337, 323G and 327G, which induced the clearest Th2 cytokine profiles, were not the most efficient to prime cell help for the induction of anti-hapten antibodies. For CTL induction, OVA323–337-derived peptides, inducing a Th1-like profile, required a lower dose (5 nmol) than Th0 peptides (50 nmol). The dose of 50 nmol was detrimental for Th1-like peptides. Interestingly, IFN- primed by the THd correlated significantly with that induced by the TCd (P < 0.01).
Keywords: antibody, antigen, cytotoxicity, epitope, peptide, Th1, Th2, TCR