title: Presentation of lipopeptide by dendritic cells induces anti-tumor responses via an endocytosis-independent pathway in vivo.
abstract: Cross-presentation by DCs is the major mechanism by which exogenous antigens activate CTLs. However, the mechanisms of entry and presentation of vaccine peptides by DCs remain unclear. In this study, we determined that the mechanisms of antigen presentation differed between nonlipidated and monopalmitoylated peptide antigens. We found that a nonlipidated long peptide could be taken up by DCs and that the peptide could be colocalized with early endosomes. The uptake of nonlipidated peptides by DCs was inhibited at low temperatures or by the depolymerization of actin filaments or microtubules. In contrast, lipidated peptides were internalized by DCs at low temperatures, and internalization was not inhibited when actin filaments or microtubules were depolymerized. Moreover, lipidated peptide, but not nonlipidated peptide, was internalized by nonphagocytic Jurkat cells. The endosomal/lysosomal and proteasomal degradation pathways were necessary for nonlipidated presentation leading to the activation of CD8(+) T cells, but the proteasomal degradation pathway alone was sufficient to process lipidated peptides for MHC class I presentation. We further found that lipidated peptides could enhance peptide-specific T cell responses in vitro and in vivo and induced stronger antitumor responses than nonlipidated peptides. Taken together, our results demonstrate that DCs present lipidated peptides through an endocytosis-independent pathway to promote strong anti-tumor effects in vivo.
authors.affiliation: Vaccine Research and Development Center, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
authors.forename: Ying-Chyi
authors.initials: YC
authors.lastname: Song
authors.forename: Ai-Hsiang
authors.initials: AH
authors.lastname: Chou
authors.forename: Atthachai
authors.initials: A
authors.lastname: Homhuan
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
authors.forename: Sheng-Kuo
authors.initials: SK
authors.lastname: Chiang
authors.forename: Kuan-Yin
authors.initials: KY
authors.lastname: Shen
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Chuang
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Leng
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Tao
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D055666:Lipopeptides / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D055666:Lipopeptides; D046988:Proteasome Endopeptidase Complex