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. 1993 Jan;67(1):75–81. doi: 10.1128/jvi.67.1.75-81.1993

Susceptibility to measles virus-induced encephalitis in mice correlates with impaired antigen presentation to cytotoxic T lymphocytes.

S Niewiesk 1, U Brinckmann 1, B Bankamp 1, S Sirak 1, U G Liebert 1, V ter Meulen 1
PMCID: PMC237339  PMID: 8093223

Abstract

In measles virus (MV) infection in humans, meningitis and encephalitis are important complications. However, little is known of the pathogenesis of MV encephalitis, in particular about the role of the immune response. We have examined the role of cytotoxic T lymphocytes (CTL) in a mouse model of MV-induced encephalitis. We report here that the resistance of inbred strains of mice to MV-induced encephalitis correlated with the major histocompatibility complex (MHC) haplotype and that only resistant mouse strains mounted an effective CTL response to MV. Mice with low susceptibility to MV infection, such as the BALB/c strain (H-2d), generated CTL, whereas the highly susceptible strains, C3H (H-2k) and C57BL/6 (H-2b), revealed very poor CTL responses. MV-induced CTL were usually CD8+, and the generation of these cells was independent of the route of inoculation or the time postinfection. CD4+ T cells were generally only weakly lytic. The nucleocapsid protein was the major target antigen for CTL in BALB/c mice, although in some experiments the hemagglutinin was also recognized. CTL from C3H and C57BL/6 mice did not lyse MV-infected target cells. However, targets infected with vaccinia virus recombinants expressing the nucleocapsid protein or hemagglutinin were lysed, but levels of cytotoxicity were still low. Experiments using target cells transfected with single MHC class I genes suggested inefficient antigen presentation of MV proteins by the MHC molecules of the H-2k and H-2b haplotypes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Askonas B. A., Taylor P. M., Esquivel F. Cytotoxic T cells in influenza infection. Ann N Y Acad Sci. 1988;532:230–237. doi: 10.1111/j.1749-6632.1988.tb36342.x. [DOI] [PubMed] [Google Scholar]
  2. Baczko K., Liebert U. G., Billeter M., Cattaneo R., Budka H., ter Meulen V. Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis. J Virol. 1986 Aug;59(2):472–478. doi: 10.1128/jvi.59.2.472-478.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bankamp B., Brinckmann U. G., Reich A., Niewiesk S., ter Meulen V., Liebert U. G. Measles virus nucleocapsid protein protects rats from encephalitis. J Virol. 1991 Apr;65(4):1695–1700. doi: 10.1128/jvi.65.4.1695-1700.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brinckmann U. G., Bankamp B., Reich A., ter Meulen V., Liebert U. G. Efficacy of individual measles virus structural proteins in the protection of rats from measles encephalitis. J Gen Virol. 1991 Oct;72(Pt 10):2491–2500. doi: 10.1099/0022-1317-72-10-2491. [DOI] [PubMed] [Google Scholar]
  5. Burgert H. G., Kvist S. An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens. Cell. 1985 Jul;41(3):987–997. doi: 10.1016/s0092-8674(85)80079-9. [DOI] [PubMed] [Google Scholar]
  6. Cattaneo R., Rebmann G., Baczko K., ter Meulen V., Billeter M. A. Altered ratios of measles virus transcripts in diseased human brains. Virology. 1987 Oct;160(2):523–526. doi: 10.1016/0042-6822(87)90031-6. [DOI] [PubMed] [Google Scholar]
  7. Cerundolo V., Alexander J., Anderson K., Lamb C., Cresswell P., McMichael A., Gotch F., Townsend A. Presentation of viral antigen controlled by a gene in the major histocompatibility complex. Nature. 1990 May 31;345(6274):449–452. doi: 10.1038/345449a0. [DOI] [PubMed] [Google Scholar]
  8. Christinck E. R., Luscher M. A., Barber B. H., Williams D. B. Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis. Nature. 1991 Jul 4;352(6330):67–70. doi: 10.1038/352067a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Falk K., Rötzschke O., Rammensee H. G. Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature. 1990 Nov 15;348(6298):248–251. doi: 10.1038/348248a0. [DOI] [PubMed] [Google Scholar]
  12. Gooding L. R. Characterization of a progressive tumor from C3H fibroblasts transformed in vitro with SV40 virus. Immunoresistance in vivo correlates with phenotypic loss of H-2Kk. J Immunol. 1982 Sep;129(3):1306–1312. [PubMed] [Google Scholar]
  13. Gotch F., Rothbard J., Howland K., Townsend A., McMichael A. Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2. 1987 Apr 30-May 6Nature. 326(6116):881–882. doi: 10.1038/326881a0. [DOI] [PubMed] [Google Scholar]
  14. Gregory C. D., Murray R. J., Edwards C. F., Rickinson A. B. Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance. J Exp Med. 1988 Jun 1;167(6):1811–1824. doi: 10.1084/jem.167.6.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haddada H., Sogn J. A., Coligan J. E., Carbone M., Dixon K., Levine A. S., Lewis A. M., Jr Viral gene inhibition of class I major histocompatibility antigen expression: not a general mechanism governing the tumorigenicity of adenovirus type 2-, adenovirus type 12-, and simian virus 40-transformed Syrian hamster cells. J Virol. 1988 Aug;62(8):2755–2761. doi: 10.1128/jvi.62.8.2755-2761.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harding C. V., Unanue E. R. Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T-cell stimulation. Nature. 1990 Aug 9;346(6284):574–576. doi: 10.1038/346574a0. [DOI] [PubMed] [Google Scholar]
  17. Jacobson S., Richert J. R., Biddison W. E., Satinsky A., Hartzman R. J., McFarland H. F. Measles virus-specific T4+ human cytotoxic T cell clones are restricted by class II HLA antigens. J Immunol. 1984 Aug;133(2):754–757. [PubMed] [Google Scholar]
  18. Johnson R. T. The pathogenesis of acute viral encephalitis and postinfectious encephalomyelitis. J Infect Dis. 1987 Mar;155(3):359–364. doi: 10.1093/infdis/155.3.359. [DOI] [PubMed] [Google Scholar]
  19. Joly E., Mucke L., Oldstone M. B. Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science. 1991 Sep 13;253(5025):1283–1285. doi: 10.1126/science.1891717. [DOI] [PubMed] [Google Scholar]
  20. Lehmann-Grube F., Moskophidis D., Löhler J. Recovery from acute virus infection. Role of cytotoxic T lymphocytes in the elimination of lymphocytic choriomeningitis virus from spleens of mice. Ann N Y Acad Sci. 1988;532:238–256. doi: 10.1111/j.1749-6632.1988.tb36343.x. [DOI] [PubMed] [Google Scholar]
  21. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Liebert U. G., Baczko K., Budka H., ter Meulen V. Restricted expression of measles virus proteins in brains from cases of subacute sclerosing panencephalitis. J Gen Virol. 1986 Nov;67(Pt 11):2435–2444. doi: 10.1099/0022-1317-67-11-2435. [DOI] [PubMed] [Google Scholar]
  23. Liebert U. G., Linington C., ter Meulen V. Induction of autoimmune reactions to myelin basic protein in measles virus encephalitis in Lewis rats. J Neuroimmunol. 1988 Jan;17(2):103–118. doi: 10.1016/0165-5728(88)90018-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Liebert U. G., ter Meulen V. Virological aspects of measles virus-induced encephalomyelitis in Lewis and BN rats. J Gen Virol. 1987 Jun;68(Pt 6):1715–1722. doi: 10.1099/0022-1317-68-6-1715. [DOI] [PubMed] [Google Scholar]
  25. Long E. O., Jacobson S. Pathways of viral antigen processing and presentation to CTL: defined by the mode of virus entry? Immunol Today. 1989 Feb;10(2):45–48. doi: 10.1016/0167-5699(89)90303-4. [DOI] [PubMed] [Google Scholar]
  26. Masucci M. G., Torsteindottir S., Colombani J., Brautbar C., Klein E., Klein G. Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4567–4571. doi: 10.1073/pnas.84.13.4567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Morrison L. A., Braciale V. L., Braciale T. J. Antigen form influences induction and frequency of influenza-specific class I and class II MHC-restricted cytolytic T lymphocytes. J Immunol. 1988 Jul 15;141(2):363–368. [PubMed] [Google Scholar]
  28. Murray N., McMichael A. Antigen presentation in virus infection. Curr Opin Immunol. 1992 Aug;4(4):401–407. doi: 10.1016/s0952-7915(06)80030-0. [DOI] [PubMed] [Google Scholar]
  29. Nash A. A., Jayasuriya A., Phelan J., Cobbold S. P., Waldmann H., Prospero T. Different roles for L3T4+ and Lyt 2+ T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system. J Gen Virol. 1987 Mar;68(Pt 3):825–833. doi: 10.1099/0022-1317-68-3-825. [DOI] [PubMed] [Google Scholar]
  30. Oldstone M. B., Blount P., Southern P. J., Lampert P. W. Cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system. Nature. 1986 May 15;321(6067):239–243. doi: 10.1038/321239a0. [DOI] [PubMed] [Google Scholar]
  31. Openshaw P. J., Anderson K., Wertz G. W., Askonas B. A. The 22,000-kilodalton protein of respiratory syncytial virus is a major target for Kd-restricted cytotoxic T lymphocytes from mice primed by infection. J Virol. 1990 Apr;64(4):1683–1689. doi: 10.1128/jvi.64.4.1683-1689.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Puddington L., Bevan M. J., Rose J. K., Lefrançois L. N protein is the predominant antigen recognized by vesicular stomatitis virus-specific cytotoxic T cells. J Virol. 1986 Nov;60(2):708–717. doi: 10.1128/jvi.60.2.708-717.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Rötzschke O., Falk K. Naturally-occurring peptide antigens derived from the MHC class-I-restricted processing pathway. Immunol Today. 1991 Dec;12(12):447–455. doi: 10.1016/0167-5699(91)90018-O. [DOI] [PubMed] [Google Scholar]
  35. Schumacher T. N., De Bruijn M. L., Vernie L. N., Kast W. M., Melief C. J., Neefjes J. J., Ploegh H. L. Peptide selection by MHC class I molecules. Nature. 1991 Apr 25;350(6320):703–706. doi: 10.1038/350703a0. [DOI] [PubMed] [Google Scholar]
  36. Shimonkevitz R., Kappler J., Marrack P., Grey H. Antigen recognition by H-2-restricted T cells. I. Cell-free antigen processing. J Exp Med. 1983 Aug 1;158(2):303–316. doi: 10.1084/jem.158.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Spies T., Bresnahan M., Bahram S., Arnold D., Blanck G., Mellins E., Pious D., DeMars R. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature. 1990 Dec 20;348(6303):744–747. doi: 10.1038/348744a0. [DOI] [PubMed] [Google Scholar]
  38. Townsend A., Bastin J., Gould K., Brownlee G., Andrew M., Coupar B., Boyle D., Chan S., Smith G. Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen. J Exp Med. 1988 Oct 1;168(4):1211–1224. doi: 10.1084/jem.168.4.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Vaessen R. T., Houweling A., van der Eb A. J. Post-transcriptional control of class I MHC mRNA expression in adenovirus 12-transformed cells. Science. 1987 Mar 20;235(4795):1486–1488. doi: 10.1126/science.3823900. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Van Noort J. M., Boon J., Van der Drift A. C., Wagenaar J. P., Boots A. M., Boog C. J. Antigen processing by endosomal proteases determines which sites of sperm-whale myoglobin are eventually recognized by T cells. Eur J Immunol. 1991 Sep;21(9):1989–1996. doi: 10.1002/eji.1830210904. [DOI] [PubMed] [Google Scholar]
  43. Vitiello A., Marchesini D., Furze J., Sherman L. A., Chesnut R. W. Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex. J Exp Med. 1991 Apr 1;173(4):1007–1015. doi: 10.1084/jem.173.4.1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Vitiello A., Potter T. A., Sherman L. A. The role of beta 2-microglobulin in peptide binding by class I molecules. Science. 1990 Dec 7;250(4986):1423–1426. doi: 10.1126/science.2124002. [DOI] [PubMed] [Google Scholar]
  45. Yap K. L., Ada G. L. Cytotoxic T cells in the lungs of mice infected with an influenza A virus. Scand J Immunol. 1978;7(1):73–80. doi: 10.1111/j.1365-3083.1978.tb00428.x. [DOI] [PubMed] [Google Scholar]
  46. Yewdell J. W., Bennink J. R., Eager K. B., Ricciardi R. P. CTL recognition of adenovirus-transformed cells infected with influenza virus: lysis by anti-influenza CTL parallels adenovirus-12-induced suppression of class I MHC molecules. Virology. 1988 Jan;162(1):236–238. doi: 10.1016/0042-6822(88)90413-8. [DOI] [PubMed] [Google Scholar]
  47. van Binnendijk R. S., Poelen M. C., Kuijpers K. C., Osterhaus A. D., Uytdehaag F. G. The predominance of CD8+ T cells after infection with measles virus suggests a role for CD8+ class I MHC-restricted cytotoxic T lymphocytes (CTL) in recovery from measles. Clonal analyses of human CD8+ class I MHC-restricted CTL. J Immunol. 1990 Mar 15;144(6):2394–2399. [PubMed] [Google Scholar]
  48. van Binnendijk R. S., Poelen M. C., de Vries P., Voorma H. O., Osterhaus A. D., Uytdehaag F. G. Measles virus-specific human T cell clones. Characterization of specificity and function of CD4+ helper/cytotoxic and CD8+ cytotoxic T cell clones. J Immunol. 1989 Apr 15;142(8):2847–2854. [PubMed] [Google Scholar]

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