This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01720-06v1 81/3/1319    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leclerc, D. Articles by Lapointe, R. Search for Related Content PubMed PubMed Citation Articles by Leclerc, D. Articles by Lapointe, R.

Proteasome-Independent Major Histocompatibility Complex Class I Cross-Presentation Mediated by Papaya Mosaic Virus-Like Particles Leads to Expansion of Specific Human T Cells

Research Centre, Centre hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame, and Institut du Cancer de Montréal, Montréal, Québec, Canada,¹ Centre de recherche en infectiologie, Pavillon Centre hospitalier de l'Université Laval (CHUL), 2705 boul. Laurier, Québec, Québec, Canada,² INRS-Institut Armand-Frappier, 531, boul. des Prairies, Laval, Québec, Canada³

Received 9 August 2006/ Accepted 8 October 2006

The development of versatile vaccine platforms is a priority that is recognized by health authorities worldwide; such platforms should induce both arms of the immune system, the humoral and cytotoxic-T-lymphocyte responses. In this study, we have established that a vaccine platform based on the coat protein of papaya mosaic virus (PapMV CP), previously shown to induce a humoral response, can induce major histocompatibility complex (MHC) class I cross-presentation of HLA-A*0201 epitopes from gp100, a melanoma antigen, and from influenza virus M1 matrix protein. PapMV proteins were able to assemble into stable virus-like particles (VLPs) in a crystalline and repetitive structure. When we pulsed HLA-A*0201⁺ antigen-presenting cells (APCs) with the recombinant PapMV FLU or gp100, we noted that antigen-specific CD8⁺ T cells were highly reactive to these APCs, demonstrating that the epitope from the VLPs were processed and loaded on the MHC class I complex. APCs were preincubated with two different proteasome inhibitors, which did not affect the efficiency of peptide presentation on MHC class I. Classical presentation from an endogenous antigen was abolished in the same conditions. Clearly, antigen presentation mediated by the PapMV system was proteasome independent. Finally, PapMV-pulsed APCs had the capacity to expand highly avid antigen-specific T cells against the influenza virus M1 HLA-A*0201 epitope when cocultured with autologous peripheral blood mononuclear cells. This study demonstrates the potential of PapMV for MHC class I cross-presentation and for the expansion of human antigen-specific T cells. It makes VLPs from PapMV CP a very attractive platform to trigger cellular responses for vaccine development against chronic infectious diseases and cancers.

Published ahead of print on 22 November 2006.

This article has been cited by other articles:

• Lacasse, P., Denis, J., Lapointe, R., Leclerc, D., Lamarre, A. (2008). Novel Plant Virus-Based Vaccine Induces Protective Cytotoxic T-Lymphocyte-Mediated Antiviral Immunity through Dendritic Cell Maturation. J. Virol. 82: 785-794 [Abstract] [Full Text]