tetano
Editor, Senior Moderator
Published ahead of print 20 June 2012, doi: 10.1128/JVI.06325-11 JVI.06325-11
A human CD4+ T cell epitope in the influenza hemagglutinin is cross-reactive to influenza A subtypes and to influenza B virus
Jenny Aurielle B. Babon1,2,
John Cruz1,
Francis A. Ennis1,2,
Liusong Yin2,3 and
Masanori Terajima1,2,#
+ Author Affiliations
1Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA
2Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA
3Department of Pathology, University of Massachusetts Medical School, Worcester, MA
ABSTRACT
The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here we describe a human CD4+ T cell epitope in the influenza HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of HA of influenza A and the HA of the influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4+ T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain and influenza B virus in cytotoxicity assays and intracellular cytokine staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMC for T cell responses specific to this epitope and found individuals who have ex vivo IFN-γ responses to this peptide epitope in ELISPOT assays. Almost all donors that responded to this epitope have the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4+ T cells which are cross-reactive to both influenza A and B viruses.
http://jvi.asm.org/content/early/20...act?related-urls=yes&legid=jvi;JVI.06325-11v1
A human CD4+ T cell epitope in the influenza hemagglutinin is cross-reactive to influenza A subtypes and to influenza B virus
Jenny Aurielle B. Babon1,2,
John Cruz1,
Francis A. Ennis1,2,
Liusong Yin2,3 and
Masanori Terajima1,2,#
+ Author Affiliations
1Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA
2Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA
3Department of Pathology, University of Massachusetts Medical School, Worcester, MA
ABSTRACT
The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here we describe a human CD4+ T cell epitope in the influenza HA that lies in the fusion peptide of the HA. This epitope is well conserved in all 16 subtypes of HA of influenza A and the HA of the influenza B virus. By stimulating peripheral blood mononuclear cells (PBMCs) from a healthy adult donor with peptides covering the entire HA protein based on the sequence of A/Japan/305/1957 (H2N2), we generated a T cell line specific to this epitope. This CD4+ T cell line recognizes target cells infected with influenza A virus seasonal H1N1 and H3N2 strains, a reassortant H2N1 strain, the 2009 pandemic H1N1 strain and influenza B virus in cytotoxicity assays and intracellular cytokine staining assays. It also lysed target cells infected with avian H5N1 virus. We screened healthy adult PBMC for T cell responses specific to this epitope and found individuals who have ex vivo IFN-γ responses to this peptide epitope in ELISPOT assays. Almost all donors that responded to this epitope have the HLA-DRB1*09 allele, a relatively common HLA allele. Although natural infection or standard vaccination may not induce strong T and B cell responses to this highly conserved epitope in the fusion peptide, it may be possible to develop a vaccination strategy to induce these CD4+ T cells which are cross-reactive to both influenza A and B viruses.
http://jvi.asm.org/content/early/20...act?related-urls=yes&legid=jvi;JVI.06325-11v1