A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro.

Abstract

Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in or adjacent to CTL epitopes. Recently, an amino acid substitution (R384G) in an HLA-B*2705-restricted CTL epitope in the influenza A virus nucleoprotein (nucleoprotein containing residues 383 to 391 [NP(383-391)]; SRYWAIRTR, where R is the residue that was mutated) was associated with escape from CTL-mediated immunity. The effect of this mutation on the in vitro influenza A virus-specific CTL response was studied. To this end, two influenza A viruses, one with and one without the NP(383-391) epitope, were constructed by reverse genetics and designated influenza viruses A/NL/94-384R and A/NL/94-384G, respectively. The absence of the HLA-B*2705-restricted CTL epitope in influenza virus A/NL/94-384G was confirmed by using (51)Cr release assays with a T-cell clone specific for the NP(383-391) epitope. In addition, peripheral blood mononuclear cells (PBMC) stimulated with influenza virus A/NL/94-384G failed to recognize HLA-B*2705-positive target cells pulsed with the original NP(383-391) peptide. The proportion of virus-specific CD8+ gamma interferon (IFN-gamma)-positive T cells in in vitro-stimulated PBMC was determined by intracellular IFN-gamma staining after restimulation with virus-infected autologous B-lymphoblastoid cell lines and C1R cell lines expressing only HLA-B*2705. The proportion of virus-specific CD8+ T cells was lower in PBMC stimulated in vitro with influenza virus A/NL/94-384G obtained from several HLA-B*2705-positive donors than in PBMC stimulated with influenza virus A/NL/94-384R. This finding indicated that amino acid variations in CTL epitopes can affect the virus-specific CTL response and that the NP(383-391) epitope is the most important HLA-B*2705-restricted epitope in the nucleoprotein of influenza A viruses.

• Authors: E G M Berkhoff, A C M Boon, N J Nieuwkoop, R A M Fouchier, K Sintnicolaas, A D M E Osterhaus, G F Rimmelzwaan
• Journal: Journal of virology (J Virol) Vol. 78 Issue 10 Pg. 5216-22 (May 2004) ISSN: 0022-538X [Print] United States
• PMID: 15113903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-B Antigens
• HLA-B*27:05 antigen
• HLA-B27 Antigen
• Immunodominant Epitopes
• NP protein, Influenza A virus
• Nucleocapsid Proteins
• Nucleoproteins
• Peptide Fragments
• RNA-Binding Proteins
• Viral Core Proteins

Topics

• Animals
• Dogs
• Epitopes, T-Lymphocyte
• HLA-B Antigens (physiology)
• HLA-B27 Antigen
• Humans
• Immunodominant Epitopes
• Influenza A virus (immunology)
• Nucleocapsid Proteins
• Nucleoproteins (immunology)
• Peptide Fragments (immunology)
• RNA-Binding Proteins
• T-Lymphocytes, Cytotoxic (immunology)
• Viral Core Proteins (immunology)