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J. Virol. doi:10.1128/JVI.01720-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Proteasome-independent MHC class I cross-presentation mediated by papaya mosaic virus-like particles leads to the 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; Centre de recherche en infectiologie, Pavillon Centre hospitalier de; l'Université Laval (CHUL), 2705 boul. Laurier, Québec, Québec, Canada; INRS-Institut Armand-Frappier, 531, boul. des Prairies, Laval, Québec, Canada

^* To whom correspondence should be addressed. Email: rejean.lapointe{at}umontreal.ca.

	Abstract

The development of versatile vaccine platforms is a priority that is recognized by health authorities worldwide, which should induce both arms of the immune system, humoral and cytotoxic T lymphocyte (CTL) 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 MHC class I cross-presentation of HLA-A*0201 epitopes, from gp100, a melanoma antigen, and from influenza M1 matrix protein. PapMV proteins were able to assemble into stable virus-like particles (VLPs), in a crystalline and repetitive structure. When we pulsed antigen-presenting cells (APCs) with the recombinant PapMV FLU or gp100 on HLA-A*0201⁺, 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 pre-incubated with 2 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 M1 HLA-A*0201 epitope when co-cultured 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.

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