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PLoS One. 2021 Dec 31;16(12):e0261987. doi: 10.1371/journal.pone.0261987. eCollection 2021.

MHC class I antigen cross-presentation mediated by PapMV nanoparticles in human antigen-presenting cells is dependent on autophagy.

PloS one

David Possamaï, Laïla-Aïcha Hanafi, Angélique Bellemare-Pelletier, Katia Hamelin, Paméla Thébault, Marie-Josée Hébert, Étienne Gagnon, Denis Leclerc, Réjean Lapointe

Affiliations

  1. Centre de recherche du Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
  2. Institut de Recherche en Immunologie et Cancérologie, Montréal, Québec, Canada.
  3. Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
  4. Centre de recherche en infectiologie, Centre hospitalier universitaire de Québec, Québec, Québec, Canada.
  5. Département de Microbiologie, Infectiologie et Immunologie, Université Laval, Québec, Québec, Canada.
  6. Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada.

PMID: 34972158 PMCID: PMC8719699 DOI: 10.1371/journal.pone.0261987

Abstract

Nanoparticles made of the coat protein of papaya mosaic virus (PapMV) and a single-strand RNA were previously shown to be an efficient antigen presentation system for the trigger of cellular immunity. Engineering of PapMV nano with a cytotoxic T lymphocyte epitope was previously shown activating specific T lymphocytes through a proteasome-independent major histocompatibility complex class I (MHC-I) cross-presentation. In this study, we provide new insights into the mechanism of the MHC-I cross-presentation mediated by PapMV nanoparticles. We demonstrate that PapMV nanoparticles do not require the transporter associated with antigen presentation (TAP), but rather depend on lysosome acidification and cathepsin S protease activity for presentation of the T cell epitope. We have also linked the induction of autophagy with this vacuolar MHC-I cross-presentation process. Interestingly, autophagy is induced in antigen-presenting cells after PapMV nanoparticles exposure and inhibition of autophagy reduce MHC-I cross-presentation. This study demonstrates that autophagy is associated with TAP- and proteasome-independent MHC-I cross-presentation. A deeper understanding of the autophagy-dependent MHC-I cross-presentation will be useful in designing vaccination platforms that aim to trigger an efficient cytotoxic T lymphocyte response.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: D.L. is the founder and a shareholder of Folia Biotech. Inc., a Canadian Biotechnology Compa

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