title: A high-affinity T-helper epitope enhances peptide-pulsed dendritic cell-based vaccine.
abstract: The NV epitope, a dominant helper determinant from the circumsporozoite antigen of Plasmodium falciparum, is strongly immunogenic and can provide help for cytotoxic T-lymphocyte (CTL) activation. In this study, we evaluated whether the addition of NV peptide can augment the efficacy of peptide-pulsed dendritic cell (DC) immunization in vivo. Using B16 melanoma as tumor model, we demonstrated that DCs pulsed with both NV and gp100 (a melanoma-specific antigen) peptide enhanced immune priming and protection from tumor challenge in vivo. Further, we showed the mechanisms of the NV epitope that help CTL activation; MHC-II-restricted NV peptide induced dramatically more effective helper cells, with a higher level of CD40L expression and IFN-γ production, which, in turn, more effectively conditioned DCs for CTL activation. The improved helper cells also induced greater IL-12 production by DCs, accounting for the reciprocal T-helper polarization to Th1, and increased the expression of costimulatory molecules. Collectively, these findings demonstrate that NV peptide in addition to tumor antigen-pulsed DC immunizations augment helper cell activation, which in turn promotes maturation of DC, and enhance in vivo antitumor activity.
authors: Key Laboratory of Molecular Medicine of Ministry of Education, Department of Immunology of Shanghai Medical College and Institute for Immunobiology, Fudan University, Shanghai, P.R. China.
authors: Ang
authors: A
authors: Li
authors: Sidong
authors: S
authors: Xiong
authors: Yi
authors: Y
authors: Lin
authors: Rongjun
authors: R
authors: Liu
authors: Yiwei
authors: Y
authors: Chu