Abstract
The regulatory immediate-early (IE) protein pp89 of murine cytomegalovirus induces CD8+ T lymphocytes that protect against lethal murine cytomegalovirus infection. The IE1 epitope is the only epitope of pp89 that is recognized by BALB/c cytolytic T lymphocytes (CTL). Using synthetic peptides, the optimal and minimal antigenic sequences of the IE1 epitope have been defined. To evaluate the predictive value of data obtained with synthetic peptides, recombinant vaccines encoding this single T-cell epitope were constructed using as a vector the hepatitis B virus core antigen encoded in recombinant vaccinia virus. In infected cells expressing the chimeric proteins, only IE1 epitope sequences that were recognized as synthetic peptides at concentrations lower than 10(-6) M were presented to CTL. Vaccination of mice with the recombinant vaccinia virus that encoded a chimeric protein carrying the optimal 9-amino-acid IE1 epitope sequence elicited CD8+ T lymphocytes with antiviral activity and, furthermore, protected against lethal disease. The results thus show for the first time that recombinant vaccines containing a single foreign nonameric CTL epitope can induce T-lymphocyte-mediated protective immunity.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnold B., Messerle M., Jatsch L., Küblbeck G., Koszinowski U. Transgenic mice expressing a soluble foreign H-2 class I antigen are tolerant to allogeneic fragments presented by self class I but not to the whole membrane-bound alloantigen. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1762–1766. doi: 10.1073/pnas.87.5.1762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beesley K. M., Francis M. J., Clarke B. E., Beesley J. E., Dopping-Hepenstal P. J., Clare J. J., Brown F., Romanos M. A. Expression in yeast of amino-terminal peptide fusions to hepatitis B core antigen and their immunological properties. Biotechnology (N Y) 1990 Jul;8(7):644–649. doi: 10.1038/nbt0790-644. [DOI] [PubMed] [Google Scholar]
- Bodmer H. C., Gotch F. M., McMichael A. J. Class I cross-restricted T cells reveal low responder allele due to processing of viral antigen. Nature. 1989 Feb 16;337(6208):653–655. doi: 10.1038/337653a0. [DOI] [PubMed] [Google Scholar]
- Brett S. J., Cease K. B., Berzofsky J. A. Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing. J Exp Med. 1988 Jul 1;168(1):357–373. doi: 10.1084/jem.168.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chimini G., Pala P., Sire J., Jordan B. R., Maryanski J. L. Recognition of oligonucleotide-encoded T cell epitopes introduced into a gene unrelated to the original antigen. J Exp Med. 1989 Jan 1;169(1):297–302. doi: 10.1084/jem.169.1.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Del Val M., Münch K., Reddehase M. J., Koszinowski U. H. Presentation of CMV immediate-early antigen to cytolytic T lymphocytes is selectively prevented by viral genes expressed in the early phase. Cell. 1989 Jul 28;58(2):305–315. doi: 10.1016/0092-8674(89)90845-3. [DOI] [PubMed] [Google Scholar]
- Del Val M., Volkmer H., Rothbard J. B., Jonjić S., Messerle M., Schickedanz J., Reddehase M. J., Koszinowski U. H. Molecular basis for cytolytic T-lymphocyte recognition of the murine cytomegalovirus immediate-early protein pp89. J Virol. 1988 Nov;62(11):3965–3972. doi: 10.1128/jvi.62.11.3965-3972.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Demotz S., Matricardi P. M., Irle C., Panina P., Lanzavecchia A., Corradin G. Processing of tetanus toxin by human antigen-presenting cells. Evidence for donor and epitope-specific processing pathways. J Immunol. 1989 Dec 15;143(12):3881–3886. [PubMed] [Google Scholar]
- Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979 Oct 25;281(5733):646–650. doi: 10.1038/281646a0. [DOI] [PubMed] [Google Scholar]
- Gould K., Cossins J., Bastin J., Brownlee G. G., Townsend A. A 15 amino acid fragment of influenza nucleoprotein synthesized in the cytoplasm is presented to class I-restricted cytotoxic T lymphocytes. J Exp Med. 1989 Sep 1;170(3):1051–1056. doi: 10.1084/jem.170.3.1051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jonjić S., del Val M., Keil G. M., Reddehase M. J., Koszinowski U. H. A nonstructural viral protein expressed by a recombinant vaccinia virus protects against lethal cytomegalovirus infection. J Virol. 1988 May;62(5):1653–1658. doi: 10.1128/jvi.62.5.1653-1658.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keil G. M., Ebeling-Keil A., Koszinowski U. H. Sequence and structural organization of murine cytomegalovirus immediate-early gene 1. J Virol. 1987 Jun;61(6):1901–1908. doi: 10.1128/jvi.61.6.1901-1908.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klavinskis L. S., Whitton J. L., Joly E., Oldstone M. B. Vaccination and protection from a lethal viral infection: identification, incorporation, and use of a cytotoxic T lymphocyte glycoprotein epitope. Virology. 1990 Oct;178(2):393–400. doi: 10.1016/0042-6822(90)90336-p. [DOI] [PubMed] [Google Scholar]
- Knowles B. B., Koncar M., Pfizenmaier K., Solter D., Aden D. P., Trinchieri G. Genetic control of the cytotoxic T cell response to SV40 tumor-associated specific antigen. J Immunol. 1979 May;122(5):1798–1806. [PubMed] [Google Scholar]
- Reddehase M. J., Bühring H. J., Koszinowski U. H. Cloned long-term cytolytic T-lymphocyte line with specificity for an immediate-early membrane antigen of murine cytomegalovirus. J Virol. 1986 Jan;57(1):408–412. doi: 10.1128/jvi.57.1.408-412.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reddehase M. J., Keil G. M., Koszinowski U. H. The cytolytic T lymphocyte response to the murine cytomegalovirus. II. Detection of virus replication stage-specific antigens by separate populations of in vivo active cytolytic T lymphocyte precursors. Eur J Immunol. 1984 Jan;14(1):56–61. doi: 10.1002/eji.1830140111. [DOI] [PubMed] [Google Scholar]
- Reddehase M. J., Koszinowski U. H. Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection. Nature. 1984 Nov 22;312(5992):369–371. doi: 10.1038/312369a0. [DOI] [PubMed] [Google Scholar]
- Reddehase M. J., Mutter W., Münch K., Bühring H. J., Koszinowski U. H. CD8-positive T lymphocytes specific for murine cytomegalovirus immediate-early antigens mediate protective immunity. J Virol. 1987 Oct;61(10):3102–3108. doi: 10.1128/jvi.61.10.3102-3108.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reddehase M. J., Rothbard J. B., Koszinowski U. H. A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes. Nature. 1989 Feb 16;337(6208):651–653. doi: 10.1038/337651a0. [DOI] [PubMed] [Google Scholar]
- Reddehase M. J., Weiland F., Münch K., Jonjic S., Lüske A., Koszinowski U. H. Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. J Virol. 1985 Aug;55(2):264–273. doi: 10.1128/jvi.55.2.264-273.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rötzschke O., Falk K., Deres K., Schild H., Norda M., Metzger J., Jung G., Rammensee H. G. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature. 1990 Nov 15;348(6298):252–254. doi: 10.1038/348252a0. [DOI] [PubMed] [Google Scholar]
- Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
- Townsend A., Bodmer H. Antigen recognition by class I-restricted T lymphocytes. Annu Rev Immunol. 1989;7:601–624. doi: 10.1146/annurev.iy.07.040189.003125. [DOI] [PubMed] [Google Scholar]
- Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
- Volkmer H., Bertholet C., Jonjić S., Wittek R., Koszinowski U. H. Cytolytic T lymphocyte recognition of the murine cytomegalovirus nonstructural immediate-early protein pp89 expressed by recombinant vaccinia virus. J Exp Med. 1987 Sep 1;166(3):668–677. doi: 10.1084/jem.166.3.668. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitton J. L., Oldstone M. B. Class I MHC can present an endogenous peptide to cytotoxic T lymphocytes. J Exp Med. 1989 Sep 1;170(3):1033–1038. doi: 10.1084/jem.170.3.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]