title: The immunodominant influenza matrix T cell epitope recognized in human induces influenza protection in HLA-A2/K(b) transgenic mice.
abstract: The protective efficacy of the influenza matrix protein epitope 58-66 (called M1), recognized in the context of human HLA-A2 molecules, was evaluated in a HLA-A2/K(b) transgenic mouse model of lethal influenza infection. Repeated subcutaneous immunizations with M1 increased the percentage of survival. This effect was mediated by T cells since protection was abolished following in vivo depletion of all T lymphocytes, CD8(+), or CD4(+) T cells. The survival correlated with the detection of memory CD8(+) splenocytes able to proliferate in vitro upon stimulation with M1 and to bind M1-loaded HLA-A2 dimers, as well as with M1-specific T cells in the lungs, which were directly cytotoxic to influenza-infected cells following influenza challenge. These results demonstrated for the first time that HLA-A2-restricted cytotoxic T cells specific for the major immunodominant influenza matrix epitope are protective against the infection. They encourage further in vivo evaluation of T cell epitopes recognized in the context of human MHC molecules.
authors.affiliation: Centre d'Immunologie Pierre Fabre, 5, Av. Napoléon III, 74 164, St Julien en Genevois, France. helene.plotnicky@pierre-fabre.com
authors.forename: H
authors.initials: H
authors.lastname: Plotnicky
authors.forename: D
authors.initials: D
authors.lastname: Cyblat-Chanal
authors.forename: J-P
authors.initials: JP
authors.lastname: Aubry
authors.forename: F
authors.initials: F
authors.lastname: Derouet
authors.forename: C
authors.initials: C
authors.lastname: Klinguer-Hamour
authors.forename: A
authors.initials: A
authors.lastname: Beck
authors.forename: J-Y
authors.initials: JY
authors.lastname: Bonnefoy
authors.forename: N
authors.initials: N
authors.lastname: Corvaïa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins