title: MHC class I-presented T cell epitopes identified by immunoproteomics analysis are targets for a cross reactive influenza-specific T cell response.
abstract: Influenza virus infection and the resulting complications are a significant global public health problem. Improving humoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross-protective. On the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protection against serologically distinct viruses due to recognition of cross-reactive T cell epitopes, often from internal viral proteins conserved between viral subtypes. Efforts are underway to develop a universal flu vaccine that would stimulate both the humoral and cellular immune responses leading to long-lived memory. Such a universal vaccine should target conserved influenza virus antibody and T cell epitopes that do not vary from strain to strain. In the last decade, immunoproteomics, or the direct identification of HLA class I presented epitopes, has emerged as an alternative to the motif prediction method for the identification of T cell epitopes. In this study, we used this method to uncover several cross-specific MHC class I specific T cell epitopes naturally presented by influenza A-infected cells. These conserved T cell epitopes, when combined with a cross-reactive antibody epitope from the ectodomain of influenza M2, generate cross-strain specific cell mediated and humoral immunity. Overall, we have demonstrated that conserved epitope-specific CTLs could recognize multiple influenza strain infected target cells and, when combined with a universal antibody epitope, could generate virus specific humoral and T cell responses, a step toward a universal vaccine concept. These epitopes also have potential as new tools to characterize T cell immunity in influenza infection, and may serve as part of a universal vaccine candidate complementary to current vaccines.
authors.affiliation: Immunotope, Inc., Doylestown, PA, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Testa
authors.forename: Vivekananda
authors.initials: V
authors.lastname: Shetty
authors.forename: Julie
authors.initials: J
authors.lastname: Hafner
authors.forename: Zacharie
authors.initials: Z
authors.lastname: Nickens
authors.forename: Shivali
authors.initials: S
authors.lastname: Kamal
authors.forename: Gomathinayagam
authors.initials: G
authors.lastname: Sinnathamby
authors.forename: Ramila
authors.initials: R
authors.lastname: Philip
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D002853:Chromatography, Liquid; D003429:Cross Reactions / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D056945:Hep G2 Cells; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides