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    Genome-wide screening of human T-cell epitopes in influenza A virus reveals a broad spectrum of CD4(+) T-cell responses to internal proteins, hemagglutinins, and neuraminidases

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    Authors
    Babon, Jenny Aurielle B.
    Cruz, John
    Orphin, Laura
    Pazoles, Pamela P.
    Co, Mary Dawn T.
    Ennis, Francis A.
    Terajima, Masanori
    UMass Chan Affiliations
    Center for Infectious Disease and Vaccine Research
    Document Type
    Journal Article
    Publication Date
    2009-06-16
    Keywords
    Epitopes, T-Lymphocyte; Influenza A virus; CD4-Positive T-Lymphocytes; Hemagglutinins
    Life Sciences
    Medicine and Health Sciences
    
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    http://dx.doi.org/10.1016/j.humimm.2009.06.004
    Abstract
    We performed a genome-wide screening for T-cell epitopes using synthetic peptides that encompass all of the influenza A viral proteins, including subtype variants for hemagglutinin (HA; H1, H3, and H5) and neuraminidase (NA; human and avian N1 and N2) proteins, based on the sequence information of recently circulating strains. We identified a total of 83 peptides, 54 of them novel, to which specific T cells were detectable in interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays using peripheral blood mononuclear cells from four healthy adult donors. The surface glycoproteins, HA and NA, major components of vaccines, expressed many T-cell epitopes. HA and matrix protein 1 expressed more T-cell epitopes than other viral proteins, most of which were recognized by CD4(+) T cells. We established several cytotoxic CD4(+) T-cell lines from these donors. We also analyzed H1 and H3 HA-specific T-cell responses using the peripheral blood mononuclear cells of 30 hospital workers. Fifty-three percent of donors gave a positive response to H3 HA peptides, whereas 17% gave a positive response to H1 HA peptides. Our genome-wide screening is useful in identifying T-cell epitopes and is complementary to the approach based on the predicted binding peptides to well-studied HLA-A, -B, and -DR alleles.
    Source
    Hum Immunol. 2009 Jun 11. Link to article on publisher's site
    DOI
    10.1016/j.humimm.2009.06.004
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/33068
    PubMed ID
    19524006
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    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.humimm.2009.06.004
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