MHC class I-presented T cell epitopes identified by immunoproteomics analysis are targets for a cross reactive influenza-specific T cell response

PLoS One. 2012;7(11):e48484. doi: 10.1371/journal.pone.0048484. Epub 2012 Nov 7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Influenza A virus / immunology
  • Influenza, Human / immunology*
  • Influenza, Human / virology
  • Mass Spectrometry
  • Mice
  • Mice, Transgenic
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology
  • Peptides / chemistry
  • Peptides / immunology
  • Proteomics / methods*
  • Reproducibility of Results
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

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