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An amino acid substitution in the influenza A virus hemagglutinin associated with escape from recognition by human virus-specific CD4+ T-cells
Eufemia G.M. Berkhoffa, Martina M. Geelhoed-Mierasa, Marcel Jongesa, Derek J. Smitha, b, Ron A.M. Fouchiera, Albert D.M.E. Osterhausa and Guus F. Rimmelzwaana, ,
aDepartment of Virology and Postgraduate School Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
bDepartment of Zoology, Cambridge University, Cambridge, UK
Received 21 December 2006; revised 22 February 2007; accepted 23 February 2007. Available online 8 April 2007.
Abstract
Influenza virus-specific CD4+ T-helper cells were cloned that recognized a virus strain isolated in 1981, but that failed to recognize more recent strains. The HLA-DR*1601-restricted epitope recognized was located in the hemagglutinin (HA99?113) and the naturally occurring A → V substitution at position 106 was responsible for abrogating the recognition by HA99?113-specific CD4+ T-cells. This amino acid substitution was found in influenza A/H3N2 viruses that circulated between 1999 and 2005 and did not affect recognition by virus-specific antibodies. It was speculated that influenza viruses could evade recognition by virus-specific CD4+ T-cells, at least temporarily.
Keywords: CD4+ T-cells; Escape; Influenza A virus
Eufemia G.M. Berkhoffa, Martina M. Geelhoed-Mierasa, Marcel Jongesa, Derek J. Smitha, b, Ron A.M. Fouchiera, Albert D.M.E. Osterhausa and Guus F. Rimmelzwaana, ,
aDepartment of Virology and Postgraduate School Molecular Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
bDepartment of Zoology, Cambridge University, Cambridge, UK
Received 21 December 2006; revised 22 February 2007; accepted 23 February 2007. Available online 8 April 2007.
Abstract
Influenza virus-specific CD4+ T-helper cells were cloned that recognized a virus strain isolated in 1981, but that failed to recognize more recent strains. The HLA-DR*1601-restricted epitope recognized was located in the hemagglutinin (HA99?113) and the naturally occurring A → V substitution at position 106 was responsible for abrogating the recognition by HA99?113-specific CD4+ T-cells. This amino acid substitution was found in influenza A/H3N2 viruses that circulated between 1999 and 2005 and did not affect recognition by virus-specific antibodies. It was speculated that influenza viruses could evade recognition by virus-specific CD4+ T-cells, at least temporarily.
Keywords: CD4+ T-cells; Escape; Influenza A virus