title: Endogenously expressed matrix protein M1 and nucleoprotein of influenza A are efficiently presented by class I and class II major histocompatibility complexes.
abstract: Current influenza vaccines containing primarily hypervariable haemagglutinin and neuraminidase proteins must be prepared against frequent new antigenic variants. Therefore, there is an ongoing effort to develop influenza vaccines that also elicit strong and sustained cytotoxic responses against highly conserved determinants such as the matrix (M1) protein and nucleoprotein (NP). However, their antigenic presentation properties in humans are less defined. Accordingly, we analysed MHC class I and class II presentation of endogenously processed M1 and NP in human antigen presenting cells and observed expansion of both CD8(+)- and CD4(+)-specific effector T lymphocytes secreting gamma interferon and tumour necrosis factor. Further enhancement of basal MHC-II antigenic presentation did not improve CD4(+) or CD8(+) T-cell quality based on cytokine production upon challenge, suggesting that endogenous M1 and NP MHC-II presentation is sufficient. These new insights about T-lymphocyte expansion following endogenous M1 and NP MHC-I and -II presentation will be important to design complementary heterosubtypic vaccination strategies.
authors.affiliation: Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Doucet
authors.affiliation: Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Marie-Andrée
authors.initials: MA
authors.lastname: Forget
authors.affiliation: Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Cécile
authors.initials: C
authors.lastname: Grange
authors.affiliation: INRS-Institut Armand-Frappier, University of Quebec, Laval, Canada.
authors.forename: Ronan Nicolas
authors.initials: RN
authors.lastname: Rouxel
authors.affiliation: Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arbour
authors.affiliation: INRS-Institut Armand-Frappier, University of Quebec, Laval, Canada.
authors.forename: Veronika
authors.initials: V
authors.lastname: von Messling
authors.affiliation: Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Université de Montréal and Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
mesh_terms: D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014758:Viral Core Proteins / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; C488936:M1 protein, Influenza A virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D007371:Interferon-gamma