A Mutation in the HLA-B*2705-Restricted NP383-391 Epitope Affects the Human Influenza A Virus-Specific Cytotoxic T-Lymphocyte Response In Vitro

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

Research output: Contribution to journalArticle

61 Scopus citations

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 [NP383-391]; 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 NP383-391 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 51Cr release assays with a T-cell clone specific for the NP383-391 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 NP383-391 peptide. The proportion of virus-specific CD8+ gamma interferon (IFN-γ)-positive T cells in in vitro-stimulated PBMC was determined by intracellular IFN-γ 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 NP383-391 epitope is the most important HLA-B*2705-restricted epitope in the nucleoprotein of influenza A viruses.

Original languageEnglish
Pages (from-to)5216-5222
Number of pages7
JournalJournal of virology
Volume78
Issue number10
DOIs
StatePublished - May 1 2004

Fingerprint Dive into the research topics of 'A Mutation in the HLA-B*2705-Restricted NP<sub>383-391</sub> Epitope Affects the Human Influenza A Virus-Specific Cytotoxic T-Lymphocyte Response In Vitro'. Together they form a unique fingerprint.

  • Cite this

    Berkhoff, E. G. M., Boon, A. C. M., Nieuwkoop, N. J., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., & Rimmelzwaan, G. F. (2004). A Mutation in the HLA-B*2705-Restricted NP383-391 Epitope Affects the Human Influenza A Virus-Specific Cytotoxic T-Lymphocyte Response In Vitro. Journal of virology, 78(10), 5216-5222. https://doi.org/10.1128/JVI.78.10.5216-5222.2004