Comparison of different classes of CpG-ODN in augmenting the generation of human epitope peptide-specific CTLs

Three distinct classes of CpG-oligonucleotides (ODN) (CpG-A, CpG-B and CpG-C) have been identified on the basis of differences in their structures and immune effects. To date, only CpG-B is applied for clinical treatments; however, it is still unknown which of the different CpG-ODN classes is most useful as an adjuvant for human cancer vaccine therapy. In the present study, we examined the activity of these 3 types of CpG-ODN in enhancing the induction of human peptide-specific CTLs. Our data showed that the specific cytotoxicity was augmented in the presence of CpG-A, -B and -C but not in the presence of control ODN, and the augmenting effect was most potent with CpG-A. Flow cytometric analysis showed the subpopulation of effector-memory cells in CD8+ cells was most increased with CpG-A. Furthermore, depletion of PDCs from PBMCs before stimulation with peptide and CpG-ODN completely abrogated the augmenting effect of CpG-ODN. These data indicated that the stimulation of PDCs by CpG-ODN augmented the generation of peptide-specific CTLs, and CpG-A was superior to CpG-B and CpG-C in terms of augmenting the generation of human peptide-specific CTLs in vitro.