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    Human cytotoxic T-cell responses against Epstein-Barr virus nuclear antigens demonstrated by using recombinant vaccinia viruses.

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    Authors
    Murray, R J
    Kurilla, M G
    Griffin, H M
    Brooks, J M
    Mackett, Mike
    Arrand, John R
    Rowe, M
    Burrows, S R
    Moss, D J
    Kieff, E
    Affiliation
    Department of Cancer Studies, University of Birmingham, United Kingdom.
    Issue Date
    1990-04
    
    Metadata
    Show full item record
    Abstract
    The potentially pathogenic effects of infection with Epstein-Barr virus (EBV), a B-lymphotropic agent with cell growth-transforming potential, are contained in healthy virus carriers by virus-specific cytotoxic T-lymphocyte (CTL) surveillance. The target antigens against which such CTL responses are directed are yet undefined, but the antigens probably derived from one or more of the EBV "latent" proteins constitutively expressed in virus-transformed B cells. We have analyzed target specificity of CTL responses from two EBV-immune donors that are preferentially reactive against autologous cells transformed with type A but not with type B virus isolates. Coding sequences for four EBV latent proteins with allelic polymorphism between A and B virus types--namely, the EBV nuclear antigens (EBNAs) EBNA 2, EBNA 3a, EBNA 3c, and EBNA leader protein--have been introduced into vaccinia virus vectors under control of vaccinia promoter P7.5 and used to express relevant EBNA proteins in appropriate target cells. Thus the CTL response from one donor has been mapped to type A EBNA 2 protein and from a second donor to type A EBNA 3a protein. Thereafter, a series of recombinant vaccinia viruses were constructed that carried specific internal deletions within the EBNA 2 type A coding sequence; by using these vectors, the above EBNA 2 type A-specific CTL response was shown to be directed against an epitope within a 100-amino acid fragment near the N terminus of the protein. This work clearly shows human CTL recognition of virus-coded nuclear antigens in the EBV system; moreover, it establishes an experimental approach that can be extended to all EBV latent proteins and to the more common CTL responses that cross-react against type A and type B virus isolates.
    Citation
    Human cytotoxic T-cell responses against Epstein-Barr virus nuclear antigens demonstrated by using recombinant vaccinia viruses. 1990, 87 (8):2906-10 Proc. Natl. Acad. Sci. U.S.A.
    Journal
    Proceedings of the National Academy of Sciences of the United States of America
    URI
    http://hdl.handle.net/10541/109763
    PubMed ID
    2158098
    Type
    Article
    Language
    en
    ISSN
    0027-8424
    Collections
    All Paterson Institute for Cancer Research

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