PMID- 11342606 OWN - NLM STAT- MEDLINE DCOM- 20010809 LR - 20210102 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 166 IP - 10 DP - 2001 May 15 TI - Human dendritic cells are activated by chimeric human papillomavirus type-16 virus-like particles and induce epitope-specific human T cell responses in vitro. PG - 5917-24 AB - Human papillomavirus (HPV)-derived chimeric virus-like particles (VLPs) are the leading candidate vaccine for the treatment or prevention of cervical cancer in humans. Dendritic cells (DCs) are the most potent inducers of immune responses and here we show for the first time evidence for binding of chimeric HPV-16 VLPs to human peripheral blood-derived DCS: Incubation of immature human DCs with VLPs for 48 h induced a significant up-regulation of the CD80 and CD83 molecules as well as secretion of IL-12. Confocal microscopy analysis revealed that cell surface-bound chimeric VLPs were taken up by DCS: Moreover, DCs loaded with chimeric HPV-16 L1L2-E7 VLPs induced an HLA-*0201-restricted human T cell response in vitro specific for E7-derived peptides. These results clearly demonstrate that immature human DCs are fully activated by chimeric HPV-16 VLPs and subsequently are capable of inducing endogenously processed epitope-specific human T cell responses in vitro. Overall, these findings could explain the high immunogenicity and efficiency of VLPs as vaccines. FAU - Rudolf, M P AU - Rudolf MP AD - Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA. FAU - Fausch, S C AU - Fausch SC FAU - Da Silva, D M AU - Da Silva DM FAU - Kast, W M AU - Kast WM LA - eng GR - P01 CA74182/CA/NCI NIH HHS/United States GR - R01 CA74397/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Capsid Proteins) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (L2 protein, Human papillomavirus type 16) RN - 0 (Lipopolysaccharides) RN - 0 (Oncogene Proteins, Viral) RN - 0 (Papillomavirus E7 Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (oncogene protein E7, Human papillomavirus type 16) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Antigen Presentation/genetics MH - Capsid/genetics/immunology/metabolism MH - *Capsid Proteins MH - Cells, Cultured MH - Dendritic Cells/*immunology/metabolism/*virology MH - Epitopes, T-Lymphocyte/genetics/*immunology/metabolism MH - Humans MH - Interleukin-12/metabolism MH - Lipopolysaccharides/immunology MH - Monocytes/immunology/metabolism/virology MH - Oncogene Proteins, Viral/genetics/immunology/metabolism MH - Papillomaviridae/genetics/*immunology MH - Papillomavirus E7 Proteins MH - Peptide Mapping MH - Protein Binding/genetics/immunology MH - Recombinant Fusion Proteins/*immunology MH - T-Lymphocytes, Cytotoxic/*immunology/metabolism MH - Tumor Necrosis Factor-alpha/immunology MH - Virion/genetics/*immunology EDAT- 2001/05/09 10:00 MHDA- 2001/08/10 10:01 CRDT- 2001/05/09 10:00 PHST- 2001/05/09 10:00 [pubmed] PHST- 2001/08/10 10:01 [medline] PHST- 2001/05/09 10:00 [entrez] AID - 10.4049/jimmunol.166.10.5917 [doi] PST - ppublish SO - J Immunol. 2001 May 15;166(10):5917-24. doi: 10.4049/jimmunol.166.10.5917.