Yellow fever virus 17D envelope and NS3 proteins are major targets of the antiviral T cell response in mice

Virology. 2002 Apr 25;296(1):117-24. doi: 10.1006/viro.2002.1432.

Abstract

The yellow fever virus 17D vaccine strain is one of the most effective and safe vaccines available. The immune response after immunization is characterized by long-lasting high titers of neutralizing antibodies. Here, we have initiated a characterization of YFV-17D-specific cellular immune responses. This study makes three points. First, we have identified two CD8 T cell epitopes and one CD4 T cell epitope. An H-2Kb-restricted dominant epitope was mapped in the NS3 protein, whereas the viral envelope protein harbored an H-2Db-restricted subdominant epitope and the I-Ab-restricted CD4 T cell epitope. Second, illustrating the concept of immunodomination, we found that after abrogation of the dominant response in H-2Kb knockout mice, the frequencies of T cells recognizing the subdominant Db-restricted epitope increased dramatically. Finally, the H-2Db-restricted epitope lacks the canonical Asn anchor residue at position 5, indicating that epitopes may be missed by strict application of the H-2Db-binding motif. Identification of these T cell epitopes will facilitate studies on the cellular immunity against YFV-based expression or immunization vectors.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Count
  • Cells, Cultured
  • Epitopes / analysis
  • Female
  • Flow Cytometry
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • Immunity, Cellular
  • Interferon-gamma / analysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Spleen / cytology
  • Spleen / immunology
  • Time Factors
  • Viral Envelope Proteins / immunology*
  • Viral Nonstructural Proteins / immunology*
  • Yellow Fever / immunology*
  • Yellow Fever / prevention & control
  • Yellow Fever Vaccine / administration & dosage
  • Yellow fever virus / immunology*
  • Yellow fever virus / metabolism

Substances

  • CD4 Antigens
  • Epitopes
  • H-2 Antigens
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins
  • Yellow Fever Vaccine
  • yellow fever virus envelope protein E
  • Interferon-gamma