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: James S Testa, Vivekananda Shetty, Julie Hafner, Zacharie Nickens, Shivali Kamal, Gomathinayagam Sinnathamby, Ramila Philip
• Journal: PloS one (PLoS One) Vol. 7 Issue 11 Pg. e48484 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23144892 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Epitopes, T-Lymphocyte
• Histocompatibility Antigens Class I
• Peptides

Topics

• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• Antigen Presentation (immunology)
• Chromatography, Liquid
• Cross Reactions (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Hep G2 Cells
• Histocompatibility Antigens Class I (chemistry, immunology)
• Humans
• Influenza A virus (immunology)
• Influenza, Human (immunology, virology)
• Mass Spectrometry
• Mice
• Mice, Transgenic
• Orthomyxoviridae Infections (immunology, virology)
• Peptides (chemistry, immunology)
• Proteomics (methods)
• Reproducibility of Results
• T-Lymphocytes, Cytotoxic (immunology)