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High diversitiy of human CD 4+ recognizing up to 30 epitopes

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  • High diversitiy of human CD 4+ recognizing up to 30 epitopes

    David H. Smith

    Direct ex vivo analyses in HLA-DR1 transgenic mice reveal an exceptionally broad pattern of immunodominance in the primary HLA-DR1 restricted CD4 T cell response to influenza hemagglutinin
    .

    J Virol. 2007 May 16;


    Richards KA, Chaves FA, Krafcik F, Topham DJ, Lazarski CA, Sant AJ.

    David H. Smith Center for Vaccine Biology and Immunology, Aab Institute, and Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642.

    The recent threat of an avian influenza pandemic has generated significant interest in enhancing our understanding of the events that dictate protective immunity to influenza and in generation of vaccines that can induce heterosubtypic immunity. Although antigen-specific CD4 T cells are known to play a key role in protective immunity to influenza through provision of help to B cells and CD8 T cells, little is known about the specificity and diversity of CD4 T cells elicited after infection, particularly those elicited in humans. In this study, we used HLA-DR transgenic mice to directly and comprehensively identify the specificity of HA-specific CD4 T cells restricted to a human class II molecule that are elicited following intranasal infection with a strain of influenza virus that has been endemic in US human populations for the last decade. Our results reveal a surprising degree of diversity of influenza-specific CD4 T cells. As many as 30 different peptides, spanning the entire HA protein, were recognized by CD4 T cells, including epitopes genetically conserved among H1, H2 and H5 influenza A viruses. We also compared three widely used MHC class II algorithms to predict HLA-DR binding peptides and find these as yet inadequate for identifying influenza-derived epitopes. The results of these studies offer key insights into the spectrum of peptides recognized by HLA-DR-restricted CD4 T cells that may be the focus of immune responses to infection or to experimental or clinical vaccines in humans.

    PMID: 17507491 [PubMed - as supplied by publisher]

  • #2
    Re: High diversitiy of human CD 4+ recognizing up to 30 epitopes

    so, this seems to be in favour of prepandemic vaccine
    vs. pandemic one (?)

    make me wonder, how the seasonal H3N2 can escape immunity and vaccination
    I'm interested in expert panflu damage estimates
    my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

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