title: pDCs efficiently process synthetic long peptides to induce functional virus- and tumour-specific T-cell responses.
abstract: Robust cell-mediated immunity is required for immune control of tumours and protection from viral infections, with both CD4(+) and CD8(+) T cells playing a pivotal role. Synthetic long peptides (SLPs) represent an attractive way to induce such combined responses, as they contain both class I and class II epitopes. The ability of plasmacytoid dendritic cells (pDCs) to cross-present SLPs has not yet been investigated; yet, pDCs play a critical role in shaping immune responses and have emerged as novel vectors for immunotherapy. Using overlapping 15-mer peptide pools covering the entire sequence of CMVpp65 and MelA, representing a viral disease (cytomegalovirus, CMV) and a tumour (melanoma), respectively, we showed that human pDCs can effectively process SLPs. Our results demonstrated that pDCs potently cross-present virus- and tumour-derived SLPs and cross-prime broad-ranging, effective and long-lived CD4(+) and CD8(+) T-cell responses, triggering more efficient immune responses than short peptide loaded pDCs. This ability required intracellular processing by the proteasome and was enhanced by co-exposure to TLR7/9-L. Combining SLPs with pDCs represents a powerful immunotherapeutic strategy to elicit potent immune responses, which are required for clinical success in cancers and viral infections.
authors.affiliation: R&D Laboratory, Etablissement Français du Sang Rhone-Alpes, Grenoble, France; Immunobiology & Immunotherapy of Cancers, University Joseph Fourier, Grenoble, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Aspord
authors.forename: Claire
authors.initials: C
authors.lastname: Leloup
authors.forename: Sabine
authors.initials: S
authors.lastname: Reche
authors.forename: Joel
authors.initials: J
authors.lastname: Plumas
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D010455:Peptides
keywords: Cancer; Cross-presentation; Long peptides; Plasmacytoid dendritic cells; Viral infection