pDCs efficiently process synthetic long peptides to induce functional virus- and tumour-specific T-cell responses.
Eur J Immunol
; 44(10): 2880-92, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-25043392
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.
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Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Viroses
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Antígenos de Neoplasias
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Neoplasias
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Antígenos Virais
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article