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. 1996 May;70(5):3252–3257. doi: 10.1128/jvi.70.5.3252-3257.1996

Specificity of the H-2 L(d)-restricted cytotoxic T-lymphocyte response to the mouse hepatitis virus nucleocapsid protein.

C C Bergmann 1, S A Stohlman 1
PMCID: PMC190190  PMID: 8627807

Abstract

Cytotoxic T lymphocytes provide protection against persistent infection of the central nervous system by the JHM strain of mouse hepatitis virus. In BALB/c (H-2d) mice, the dominant response is directed against an Ld-restricted peptide in the nucleocapsid protein (APTAGAFFF). Characterization of the fine specificity of this response revealed that the predicted anchor residues at positions 2 and 9 were the most critical for class I binding. Amino acids at positions 7 and 8 were identified as T-cell receptor contact residues. Virus-induced cytotoxic T lymphocytes to other Ld motif-containing nucleocapsid peptides were not detected, despite the identification of two epitopes with reduced Ld affinity. These data suggest that mutations within four residues of the dominant epitope could contribute to the persistence of the JHM strain of mouse hepatitis virus.

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Selected References

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  1. Adami C., Pooley J., Glomb J., Stecker E., Fazal F., Fleming J. O., Baker S. C. Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA. Virology. 1995 Jun 1;209(2):337–346. doi: 10.1006/viro.1995.1265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bastin J., Rothbard J., Davey J., Jones I., Townsend A. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes. J Exp Med. 1987 Jun 1;165(6):1508–1523. doi: 10.1084/jem.165.6.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beauverger P., Buckland R., Wild F. Measles virus hemagglutinin induces an Ld-restricted CD8+ cytotoxic T lymphocyte response to two specific epitopes. Virology. 1994 Apr;200(1):281–283. doi: 10.1006/viro.1994.1187. [DOI] [PubMed] [Google Scholar]
  4. Beauverger P., Buckland R., Wild T. F. Measles virus antigens induce both type-specific and canine distemper virus cross-reactive cytotoxic T lymphocytes in mice: localization of a common Ld-restricted nucleoprotein epitope. J Gen Virol. 1993 Nov;74(Pt 11):2357–2363. doi: 10.1099/0022-1317-74-11-2357. [DOI] [PubMed] [Google Scholar]
  5. Bergmann C. C., Tong L., Cua R. V., Sensintaffar J. L., Stohlman S. A. Cytotoxic T cell repertoire selection. A single amino acid determines alternative class I restriction. J Immunol. 1994 Jun 15;152(12):5603–5612. [PubMed] [Google Scholar]
  6. Bergmann C. C., Yao Q., Lin M., Stohlman S. A. The JHM strain of mouse hepatitis virus induces a spike protein-specific Db-restricted cytotoxic T cell response. J Gen Virol. 1996 Feb;77(Pt 2):315–325. doi: 10.1099/0022-1317-77-2-315. [DOI] [PubMed] [Google Scholar]
  7. Bergmann C., McMillan M., Stohlman S. Characterization of the Ld-restricted cytotoxic T-lymphocyte epitope in the mouse hepatitis virus nucleocapsid protein. J Virol. 1993 Dec;67(12):7041–7049. doi: 10.1128/jvi.67.12.7041-7049.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bertoletti A., Sette A., Chisari F. V., Penna A., Levrero M., De Carli M., Fiaccadori F., Ferrari C. Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells. Nature. 1994 Jun 2;369(6479):407–410. doi: 10.1038/369407a0. [DOI] [PubMed] [Google Scholar]
  9. Bouvier M., Wiley D. C. Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules. Science. 1994 Jul 15;265(5170):398–402. doi: 10.1126/science.8023162. [DOI] [PubMed] [Google Scholar]
  10. Buchmeier M. J., Lewicki H. A., Talbot P. J., Knobler R. L. Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology. 1984 Jan 30;132(2):261–270. doi: 10.1016/0042-6822(84)90033-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Castro R. F., Perlman S. CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity. J Virol. 1995 Dec;69(12):8127–8131. doi: 10.1128/jvi.69.12.8127-8131.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chen W., Khilko S., Fecondo J., Margulies D. H., McCluskey J. Determinant selection of major histocompatibility complex class I-restricted antigenic peptides is explained by class I-peptide affinity and is strongly influenced by nondominant anchor residues. J Exp Med. 1994 Oct 1;180(4):1471–1483. doi: 10.1084/jem.180.4.1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Corr M., Boyd L. F., Frankel S. R., Kozlowski S., Padlan E. A., Margulies D. H. Endogenous peptides of a soluble major histocompatibility complex class I molecule, H-2Lds: sequence motif, quantitative binding, and molecular modeling of the complex. J Exp Med. 1992 Dec 1;176(6):1681–1692. doi: 10.1084/jem.176.6.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Couillin I., Culmann-Penciolelli B., Gomard E., Choppin J., Levy J. P., Guillet J. G., Saragosti S. Impaired cytotoxic T lymphocyte recognition due to genetic variations in the main immunogenic region of the human immunodeficiency virus 1 NEF protein. J Exp Med. 1994 Sep 1;180(3):1129–1134. doi: 10.1084/jem.180.3.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Del Val M., Schlicht H. J., Volkmer H., Messerle M., Reddehase M. J., Koszinowski U. H. Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope. J Virol. 1991 Jul;65(7):3641–3646. doi: 10.1128/jvi.65.7.3641-3646.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fazakerley J. K., Buchmeier M. J. Pathogenesis of virus-induced demyelination. Adv Virus Res. 1993;42:249–324. doi: 10.1016/S0065-3527(08)60087-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Germain R. N. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell. 1994 Jan 28;76(2):287–299. doi: 10.1016/0092-8674(94)90336-0. [DOI] [PubMed] [Google Scholar]
  18. Jameson S. C., Bevan M. J. Dissection of major histocompatibility complex (MHC) and T cell receptor contact residues in a Kb-restricted ovalbumin peptide and an assessment of the predictive power of MHC-binding motifs. Eur J Immunol. 1992 Oct;22(10):2663–2667. doi: 10.1002/eji.1830221028. [DOI] [PubMed] [Google Scholar]
  19. Koup R. A. Virus escape from CTL recognition. J Exp Med. 1994 Sep 1;180(3):779–782. doi: 10.1084/jem.180.3.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lewicki H. A., Von Herrath M. G., Evans C. F., Whitton J. L., Oldstone M. B. CTL escape viral variants. II. Biologic activity in vivo. Virology. 1995 Aug 20;211(2):443–450. doi: 10.1006/viro.1995.1426. [DOI] [PubMed] [Google Scholar]
  21. Lewicki H., Tishon A., Borrow P., Evans C. F., Gairin J. E., Hahn K. M., Jewell D. A., Wilson I. A., Oldstone M. B. CTL escape viral variants. I. Generation and molecular characterization. Virology. 1995 Jun 20;210(1):29–40. doi: 10.1006/viro.1995.1314. [DOI] [PubMed] [Google Scholar]
  22. Madden D. R., Garboczi D. N., Wiley D. C. The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2. Cell. 1993 Nov 19;75(4):693–708. doi: 10.1016/0092-8674(93)90490-h. [DOI] [PubMed] [Google Scholar]
  23. Moskophidis D., Zinkernagel R. M. Immunobiology of cytotoxic T-cell escape mutants of lymphocytic choriomeningitis virus. J Virol. 1995 Apr;69(4):2187–2193. doi: 10.1128/jvi.69.4.2187-2193.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Parker K. C., Bednarek M. A., Coligan J. E. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol. 1994 Jan 1;152(1):163–175. [PubMed] [Google Scholar]
  25. Rammensee H. G., Falk K., Rötzschke O. Peptides naturally presented by MHC class I molecules. Annu Rev Immunol. 1993;11:213–244. doi: 10.1146/annurev.iy.11.040193.001241. [DOI] [PubMed] [Google Scholar]
  26. Reddehase M. J., Koszinowski U. H. Redistribution of critical major histocompatibility complex and T cell receptor-binding functions of residues in an antigenic sequence after biterminal substitution. Eur J Immunol. 1991 Jul;21(7):1697–1701. doi: 10.1002/eji.1830210717. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Sadovnikova E., Zhu X., Collins S. M., Zhou J., Vousden K., Crawford L., Beverley P., Stauss H. J. Limitations of predictive motifs revealed by cytotoxic T lymphocyte epitope mapping of the human papilloma virus E7 protein. Int Immunol. 1994 Feb;6(2):289–296. doi: 10.1093/intimm/6.2.289. [DOI] [PubMed] [Google Scholar]
  29. Schirmbeck R., Melber K., Kuhröber A., Janowicz Z. A., Reimann J. Immunization with soluble hepatitis B virus surface protein elicits murine H-2 class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo. J Immunol. 1994 Feb 1;152(3):1110–1119. [PubMed] [Google Scholar]
  30. Schulz M., Aichele P., Schneider R., Hansen T. H., Zinkernagel R. M., Hengartner H. Major histocompatibility complex binding and T cell recognition of a viral nonapeptide containing a minimal tetrapeptide. Eur J Immunol. 1991 May;21(5):1181–1185. doi: 10.1002/eji.1830210513. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Sette A., Vitiello A., Reherman B., Fowler P., Nayersina R., Kast W. M., Melief C. J., Oseroff C., Yuan L., Ruppert J. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol. 1994 Dec 15;153(12):5586–5592. [PubMed] [Google Scholar]
  33. Shibata K., Imarai M., van Bleek G. M., Joyce S., Nathenson S. G. Vesicular stomatitis virus antigenic octapeptide N52-59 is anchored into the groove of the H-2Kb molecule by the side chains of three amino acids and the main-chain atoms of the amino terminus. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3135–3139. doi: 10.1073/pnas.89.7.3135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stohlman S. A., Bergmann C. C., van der Veen R. C., Hinton D. R. Mouse hepatitis virus-specific cytotoxic T lymphocytes protect from lethal infection without eliminating virus from the central nervous system. J Virol. 1995 Feb;69(2):684–694. doi: 10.1128/jvi.69.2.684-694.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stohlman S. A., Kyuwa S., Polo J. M., Brady D., Lai M. M., Bergmann C. C. Characterization of mouse hepatitis virus-specific cytotoxic T cells derived from the central nervous system of mice infected with the JHM strain. J Virol. 1993 Dec;67(12):7050–7059. doi: 10.1128/jvi.67.12.7050-7059.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stohlman S. A., Matsushima G. K., Casteel N., Weiner L. P. In vivo effects of coronavirus-specific T cell clones: DTH inducer cells prevent a lethal infection but do not inhibit virus replication. J Immunol. 1986 Apr 15;136(8):3052–3056. [PubMed] [Google Scholar]
  37. Udaka K., Tsomides T. J., Walden P., Fukusen N., Eisen H. N. A ubiquitous protein is the source of naturally occurring peptides that are recognized by a CD8+ T-cell clone. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11272–11276. doi: 10.1073/pnas.90.23.11272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Van den Eynde B., Mazarguil H., Lethé B., Laval F., Gairin J. E. Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues on a single nonameric peptide that binds to H-2Ld and is recognized by cytotoxic T lymphocytes against mouse tumor P815. Eur J Immunol. 1994 Nov;24(11):2740–2745. doi: 10.1002/eji.1830241125. [DOI] [PubMed] [Google Scholar]
  39. Villanueva M. S., Fischer P., Feen K., Pamer E. G. Efficiency of MHC class I antigen processing: a quantitative analysis. Immunity. 1994 Sep;1(6):479–489. doi: 10.1016/1074-7613(94)90090-6. [DOI] [PubMed] [Google Scholar]
  40. 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]

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