Abstract
A synthetic peptide corresponding to an immunodominant epitope of lymphocytic choriomeningitis virus glycoprotein (LCMV GP) was used to prime or to tolerize CD8+ T cells in vivo, dependent on mode of immunization. Peptide-specific tolerance was then examined in transgenic mice expressing LCMV GP in the beta islet cells of the pancreas; these mice develop CD8+ T-cell-mediated diabetes within 8-14 days after LCMV infection. Specific peptide-induced tolerance prevented autoimmune destruction of beta islet cells and diabetes in this transgenic mouse model.
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- Adorini L., Moreno J., Momburg F., Hämmerling G. J., Guéry J. C., Valli A., Fuchs S. Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells. J Exp Med. 1991 Oct 1;174(4):945–948. doi: 10.1084/jem.174.4.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aichele P., Hengartner H., Zinkernagel R. M., Schulz M. Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide. J Exp Med. 1990 May 1;171(5):1815–1820. doi: 10.1084/jem.171.5.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Battegay M., Cooper S., Althage A., Bänziger J., Hengartner H., Zinkernagel R. M. Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates. J Virol Methods. 1991 Jun;33(1-2):191–198. doi: 10.1016/0166-0934(91)90018-u. [DOI] [PubMed] [Google Scholar]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
- Bretscher P., Cohn M. A theory of self-nonself discrimination. Science. 1970 Sep 11;169(3950):1042–1049. doi: 10.1126/science.169.3950.1042. [DOI] [PubMed] [Google Scholar]
- Buchmeier M. J., Welsh R. M., Dutko F. J., Oldstone M. B. The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv Immunol. 1980;30:275–331. doi: 10.1016/s0065-2776(08)60197-2. [DOI] [PubMed] [Google Scholar]
- Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
- Carbone F. R., Bevan M. J. Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization. J Exp Med. 1989 Mar 1;169(3):603–612. doi: 10.1084/jem.169.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clayton J. P., Gammon G. M., Ando D. G., Kono D. H., Hood L., Sercarz E. E. Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein. J Exp Med. 1989 May 1;169(5):1681–1691. doi: 10.1084/jem.169.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Magistris M. T., Alexander J., Coggeshall M., Altman A., Gaeta F. C., Grey H. M., Sette A. Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell. 1992 Feb 21;68(4):625–634. doi: 10.1016/0092-8674(92)90139-4. [DOI] [PubMed] [Google Scholar]
- Fuchs E. J., Matzinger P. B cells turn off virgin but not memory T cells. Science. 1992 Nov 13;258(5085):1156–1159. doi: 10.1126/science.1439825. [DOI] [PubMed] [Google Scholar]
- Gao X. M., Zheng B., Liew F. Y., Brett S., Tite J. Priming of influenza virus-specific cytotoxic T lymphocytes vivo by short synthetic peptides. J Immunol. 1991 Nov 15;147(10):3268–3273. [PubMed] [Google Scholar]
- Gaur A., Wiers B., Liu A., Rothbard J., Fathman C. G. Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy. Science. 1992 Nov 27;258(5087):1491–1494. doi: 10.1126/science.1279812. [DOI] [PubMed] [Google Scholar]
- HOTCHIN J. The biology of lymphocytic choriomeningitis infection: virus-induced immune disease. Cold Spring Harb Symp Quant Biol. 1962;27:479–499. doi: 10.1101/sqb.1962.027.001.046. [DOI] [PubMed] [Google Scholar]
- Hany M., Oehen S., Schulz M., Hengartner H., Mackett M., Bishop D. H., Overton H., Zinkernagel R. M. Anti-viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia-recombinant virus expressing LCMV-WE nucleoprotein or glycoprotein. Eur J Immunol. 1989 Mar;19(3):417–424. doi: 10.1002/eji.1830190302. [DOI] [PubMed] [Google Scholar]
- Kast W. M., Roux L., Curren J., Blom H. J., Voordouw A. C., Meloen R. H., Kolakofsky D., Melief C. J. Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2283–2287. doi: 10.1073/pnas.88.6.2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kyburz D., Aichele P., Speiser D. E., Hengartner H., Zinkernagel R. M., Pircher H. T cell immunity after a viral infection versus T cell tolerance induced by soluble viral peptides. Eur J Immunol. 1993 Aug;23(8):1956–1962. doi: 10.1002/eji.1830230834. [DOI] [PubMed] [Google Scholar]
- Lafferty K. J., Cunningham A. J. A new analysis of allogeneic interactions. Aust J Exp Biol Med Sci. 1975 Feb;53(1):27–42. doi: 10.1038/icb.1975.3. [DOI] [PubMed] [Google Scholar]
- MITCHISON N. A. INDUCTION OF IMMUNOLOGICAL PARALYSIS IN TWO ZONES OF DOSAGE. Proc R Soc Lond B Biol Sci. 1964 Dec 15;161:275–292. doi: 10.1098/rspb.1964.0093. [DOI] [PubMed] [Google Scholar]
- Ohashi P. S., Oehen S., Buerki K., Pircher H., Ohashi C. T., Odermatt B., Malissen B., Zinkernagel R. M., Hengartner H. Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. Cell. 1991 Apr 19;65(2):305–317. doi: 10.1016/0092-8674(91)90164-t. [DOI] [PubMed] [Google Scholar]
- Oki A., Sercarz E. T cell tolerance studied at the level of antigenic determinants. I. Latent reactivity to lysozyme peptides that lack suppressogenic epitopes can be revealed in lysozyme-tolerant mice. J Exp Med. 1985 May 1;161(5):897–911. doi: 10.1084/jem.161.5.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oldstone M. B., Whitton J. L., Lewicki H., Tishon A. Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus-specific class I-restricted H-2Db cytotoxic T lymphocytes. J Exp Med. 1988 Aug 1;168(2):559–570. doi: 10.1084/jem.168.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pircher H., Moskophidis D., Rohrer U., Bürki K., Hengartner H., Zinkernagel R. M. Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature. 1990 Aug 16;346(6285):629–633. doi: 10.1038/346629a0. [DOI] [PubMed] [Google Scholar]
- Ria F., Chan B. M., Scherer M. T., Smith J. A., Gefter M. L. Immunological activity of covalently linked T-cell epitopes. Nature. 1990 Jan 25;343(6256):381–383. doi: 10.1038/343381a0. [DOI] [PubMed] [Google Scholar]
- Romero P., Eberl G., Casanova J. L., Cordey A. S., Widmann C., Luescher I. F., Corradin G., Maryanski J. L. Immunization with synthetic peptides containing a defined malaria epitope induces a highly diverse cytotoxic T lymphocyte response. Evidence that two peptide residues are buried in the MHC molecule. J Immunol. 1992 Mar 15;148(6):1871–1878. [PubMed] [Google Scholar]
- Schulz M., Aichele P., Vollenweider M., Bobe F. W., Cardinaux F., Hengartner H., Zinkernagel R. M. Major histocompatibility complex--dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease. Eur J Immunol. 1989 Sep;19(9):1657–1667. doi: 10.1002/eji.1830190921. [DOI] [PubMed] [Google Scholar]
- Schulz M., Zinkernagel R. M., Hengartner H. Peptide-induced antiviral protection by cytotoxic T cells. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):991–993. doi: 10.1073/pnas.88.3.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. H. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. doi: 10.1126/science.2113314. [DOI] [PubMed] [Google Scholar]
- Sinha A. A., Lopez M. T., McDevitt H. O. Autoimmune diseases: the failure of self tolerance. Science. 1990 Jun 15;248(4961):1380–1388. doi: 10.1126/science.1972595. [DOI] [PubMed] [Google Scholar]
- Smilek D. E., Wraith D. C., Hodgkinson S., Dwivedy S., Steinman L., McDevitt H. O. A single amino acid change in a myelin basic protein peptide confers the capacity to prevent rather than induce experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9633–9637. doi: 10.1073/pnas.88.21.9633. [DOI] [PMC free article] [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]
- Whitton J. L., Tishon A., Lewicki H., Gebhard J., Cook T., Salvato M., Joly E., Oldstone M. B. Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity. J Virol. 1989 Oct;63(10):4303–4310. doi: 10.1128/jvi.63.10.4303-4310.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Leist T., Hengartner H., Althage A. Susceptibility to lymphocytic choriomeningitis virus isolates correlates directly with early and high cytotoxic T cell activity, as well as with footpad swelling reaction, and all three are regulated by H-2D. J Exp Med. 1985 Dec 1;162(6):2125–2141. doi: 10.1084/jem.162.6.2125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zinkernagel R. M., Pircher H. P., Ohashi P., Oehen S., Odermatt B., Mak T., Arnheiter H., Bürki K., Hengartner H. T and B cell tolerance and responses to viral antigens in transgenic mice: implications for the pathogenesis of autoimmune versus immunopathological disease. Immunol Rev. 1991 Aug;122:133–171. doi: 10.1111/j.1600-065x.1991.tb00601.x. [DOI] [PubMed] [Google Scholar]