Cross-presentation is a key function of dendritic cells (DCs), which present exogenous antigens on MHC class I molecules to prime cytotoxic T lymphocyte (CTL) responses. Here, we used synthetic mono-, di-palmitoylated peptides and non-lipidated peptide that contain CTL epitopes of HPV E7. We observed that all three peptides can be internalized by the bone marrow-derived DCs (BMDCs) but using different pathway. The mono-palmitoylated peptide can be internalized by an energyindependent pathway. The di-palmitoylated peptides internalization was facilitated by TLR2 via clathrin-mediated endocytosis. The mono-palmitoylated peptide immunization can induce T cell responses and the anti-tumor effects can be enhanced in the presence of the emulsion type adjuvant. However, the administration of di-palmitoylated peptide alone can induce anti-tumor effects through TLR2. We further demonstrated that the induction of antigen-specific CTL responses and tumor regression by dipalmitoylated peptides was transporter associated with antigen processing (TAP) independent. In addition, presentation of di-palmitoylated peptides by MHC class I molecules was blocked in the presence of an endosomal acidification inhibitor (chloroquine) or a lysosomal degradation inhibitor (Z-FL-COCHO). In summary, our data suggest that the different types of the lapidated can have different mechanisms to induce anti-tumor effects.
Date:
2018-05
Relation:
European Journal of Immunology. 2018 May;48(Suppl. 1):36.
