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dc.contributor.authorMurray, R Jen
dc.contributor.authorKurilla, M Gen
dc.contributor.authorGriffin, H Men
dc.contributor.authorBrooks, J Men
dc.contributor.authorMackett, Mikeen
dc.contributor.authorArrand, John Ren
dc.contributor.authorRowe, Men
dc.contributor.authorBurrows, S Ren
dc.contributor.authorMoss, D Jen
dc.contributor.authorKieff, Een
dc.date.accessioned2010-08-17T13:10:58Z
dc.date.available2010-08-17T13:10:58Z
dc.date.issued1990-04
dc.identifier.citationHuman 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.en
dc.identifier.issn0027-8424
dc.identifier.pmid2158098
dc.identifier.urihttp://hdl.handle.net/10541/109763
dc.description.abstractThe 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.
dc.language.isoenen
dc.subject.meshAntigens, Viral
dc.subject.meshCell Transformation, Viral
dc.subject.meshCytotoxicity, Immunologic
dc.subject.meshEpstein-Barr Virus Nuclear Antigens
dc.subject.meshHerpesvirus 4, Human
dc.subject.meshHumans
dc.subject.meshImmunoblotting
dc.subject.meshRecombination, Genetic
dc.subject.meshT-Lymphocytes, Cytotoxic
dc.subject.meshVaccinia virus
dc.subject.meshViral Proteins
dc.titleHuman cytotoxic T-cell responses against Epstein-Barr virus nuclear antigens demonstrated by using recombinant vaccinia viruses.en
dc.typeArticleen
dc.contributor.departmentDepartment of Cancer Studies, University of Birmingham, United Kingdom.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen
html.description.abstractThe 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.


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