Adoptive immunity mediated by HLA-A*0201 restricted Asp f16 peptides-specific CD8+ T cells against Aspergillus fumigatus infection

Eur J Clin Microbiol Infect Dis. 2012 Nov;31(11):3089-96. doi: 10.1007/s10096-012-1670-2. Epub 2012 Jun 14.

Abstract

Aspergillus fumigatus (A. fumigatus) is the most common pathogen of invasive aspergillosis (IA), a life-threatening infection in immunocompromised patients. Recent findings revealed that CD8+ T cells can mediate cytotoxic activity against A. fumigatus. Here, we bioinformatically identified three HLA-A*0201-restricted peptides from Asp f16, an A. fumigatus antigen which was previously shown to be involved in T cell immunity. Our immunological results demonstrated that these peptides can potently induce cytotoxic T lymphocyte (CTL) response in CD8+ T cells, thus, damaging the conidia and hyphae of A. fumigatus. Moreover, the Asp f16 peptides can also raise Th1 cell-like response, as measured by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT). Furthermore, we established an invasive pulmonary aspergillosis model in HLA-A*0201 transgenic mice. Adoptive transfer of Asp f16 peptides-specific CTL significantly extended the overall survival time in the A. fumigatus-infected immunocompromised mice. In conclusion, our results demonstrate that the Asp f16 peptides might provide immunity against invasive A. fumigatus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Adoptive Transfer
  • Allergens / immunology*
  • Animals
  • Aspergillosis / immunology*
  • Aspergillus fumigatus / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Computational Biology
  • Disease Models, Animal
  • Enzyme-Linked Immunospot Assay
  • Fungal Proteins / immunology*
  • HLA-A2 Antigen / metabolism*
  • Hyphae / immunology
  • Immunization, Passive
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spores, Fungal / immunology
  • Survival Analysis
  • Th1 Cells / immunology

Substances

  • Allergens
  • Fungal Proteins
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • allergen Asp f 16
  • Interferon-gamma