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. 1989 Apr;63(4):1756–1762. doi: 10.1128/jvi.63.4.1756-1762.1989

HLA class II-restricted presentation of cytoplasmic measles virus antigens to cytotoxic T cells.

S Jacobson 1, R P Sekaly 1, C L Jacobson 1, H F McFarland 1, E O Long 1
PMCID: PMC248439  PMID: 2784508

Abstract

To analyze the nature of the HLA class II-restricted cytotoxic T-lymphocyte (CTL) response to measles virus, murine fibroblasts were transfected with expressible cDNA clones for human HLA-DR antigen and for measles virus matrix or nucleocapsid proteins. DR-positive murine fibroblasts transfected with measles virus matrix or nucleocapsid genes were lysed by class II-restricted measles virus-specific CTL lines. Lysis was as efficient as with infected autologous B-cell lines, even though the measles virus cytoplasmic proteins were undetectable by antibodies in the transfected target cells. These results demonstrate that cytoplasmic viral antigens can be presented to CTL in the context of HLA class II antigens and that measles virus matrix and nucleocapsid proteins contribute to class II-restricted measles virus-specific CTL responses. These results also show that endogenously synthesized measles virus proteins can be efficiently presented by class II antigens. The implications of these findings for measles virus pathogenesis and for antigen processing are discussed.

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Selected References

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

  1. Bellini W. J., Englund G., Richardson C. D., Rozenblatt S., Lazzarini R. A. Matrix genes of measles virus and canine distemper virus: cloning, nucleotide sequences, and deduced amino acid sequences. J Virol. 1986 May;58(2):408–416. doi: 10.1128/jvi.58.2.408-416.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biassoni R., Ferrini S., Prigione I., Moretta A., Long E. O. CD3-negative lymphokine-activated cytotoxic cells express the CD3 epsilon gene. J Immunol. 1988 Mar 1;140(5):1685–1689. [PubMed] [Google Scholar]
  3. Braciale T. J., Braciale V. L., Winkler M., Stroynowski I., Hood L., Sambrook J., Gething M. J. On the role of the transmembrane anchor sequence of influenza hemagglutinin in target cell recognition by class I MHC-restricted, hemagglutinin-specific cytolytic T lymphocytes. J Exp Med. 1987 Sep 1;166(3):678–692. doi: 10.1084/jem.166.3.678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braciale T. J., Morrison L. A., Sweetser M. T., Sambrook J., Gething M. J., Braciale V. L. Antigen presentation pathways to class I and class II MHC-restricted T lymphocytes. Immunol Rev. 1987 Aug;98:95–114. doi: 10.1111/j.1600-065x.1987.tb00521.x. [DOI] [PubMed] [Google Scholar]
  5. Buus S., Sette A., Colon S. M., Jenis D. M., Grey H. M. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell. 1986 Dec 26;47(6):1071–1077. doi: 10.1016/0092-8674(86)90822-6. [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. Cattaneo R., Rebmann G., Schmid A., Baczko K., ter Meulen V., Billeter M. A. Altered transcription of a defective measles virus genome derived from a diseased human brain. EMBO J. 1987 Mar;6(3):681–688. doi: 10.1002/j.1460-2075.1987.tb04808.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Fleischer B., Becht H., Rott R. Recognition of viral antigens by human influenza A virus-specific T lymphocyte clones. J Immunol. 1985 Oct;135(4):2800–2804. [PubMed] [Google Scholar]
  10. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gorman C., Padmanabhan R., Howard B. H. High efficiency DNA-mediated transformation of primate cells. Science. 1983 Aug 5;221(4610):551–553. doi: 10.1126/science.6306768. [DOI] [PubMed] [Google Scholar]
  12. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  13. Jacobson S., Flerlage M. L., McFarland H. F. Impaired measles virus-specific cytotoxic T cell responses in multiple sclerosis. J Exp Med. 1985 Sep 1;162(3):839–850. doi: 10.1084/jem.162.3.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Kavathas P., Bach F. H., DeMars R. Gamma ray-induced loss of expression of HLA and glyoxalase I alleles in lymphoblastoid cells. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4251–4255. doi: 10.1073/pnas.77.7.4251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koch N., Harris A. W. Differential expression of the invariant chain in mouse tumor cells: relationship to B lymphoid development. J Immunol. 1984 Jan;132(1):12–15. [PubMed] [Google Scholar]
  17. Lamb J. R., Eckels D. D., Lake P., Woody J. N., Green N. Human T-cell clones recognize chemically synthesized peptides of influenza haemagglutinin. Nature. 1982 Nov 4;300(5887):66–69. doi: 10.1038/300066a0. [DOI] [PubMed] [Google Scholar]
  18. Laub O., Rutter W. J. Expression of the human insulin gene and cDNA in a heterologous mammalian system. J Biol Chem. 1983 May 25;258(10):6043–6050. [PubMed] [Google Scholar]
  19. 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]
  20. Long E. O., Wake C. T., Gorski J., Mach B. Complete sequence of an HLA-dR beta chain deduced from a cDNA clone and identification of multiple non-allelic DR beta chain genes. EMBO J. 1983;2(3):389–394. doi: 10.1002/j.1460-2075.1983.tb01435.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Massa P. T., Schimpl A., Wecker E., ter Meulen V. Tumor necrosis factor amplifies measles virus-mediated Ia induction on astrocytes. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7242–7245. doi: 10.1073/pnas.84.20.7242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McMichael A. J., Michie C. A., Gotch F. M., Smith G. L., Moss B. Recognition of influenza A virus nucleoprotein by human cytotoxic T lymphocytes. J Gen Virol. 1986 Apr;67(Pt 4):719–726. doi: 10.1099/0022-1317-67-4-719. [DOI] [PubMed] [Google Scholar]
  23. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  24. Meuer S. C., Hodgdon J. C., Cooper D. A., Hussey R. E., Fitzgerald K. A., Schlossman S. F., Reinherz E. L. Human cytotoxic T cell clones directed at autologous virus-transformed targets: further evidence for linkage of genetic restriction to T4 and T8 surface glycoproteins. J Immunol. 1983 Jul;131(1):186–190. [PubMed] [Google Scholar]
  25. Morrison L. A., Lukacher A. E., Braciale V. L., Fan D. P., Braciale T. J. Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med. 1986 Apr 1;163(4):903–921. doi: 10.1084/jem.163.4.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rozenblatt S., Eizenberg O., Ben-Levy R., Lavie V., Bellini W. J. Sequence homology within the morbilliviruses. J Virol. 1985 Feb;53(2):684–690. doi: 10.1128/jvi.53.2.684-690.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schmid D. S. The human MHC-restricted cellular response to herpes simplex virus type 1 is mediated by CD4+, CD8- T cells and is restricted to the DR region of the MHC complex. J Immunol. 1988 May 15;140(10):3610–3616. [PubMed] [Google Scholar]
  29. Sekaly R. P., Jacobson S., Richert J. R., Tonnelle C., McFarland H. F., Long E. O. Antigen presentation to HLA class II-restricted measles virus-specific T-cell clones can occur in the absence of the invariant chain. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1209–1212. doi: 10.1073/pnas.85.4.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sekaly R. P., Tonnelle C., Strubin M., Mach B., Long E. O. Cell surface expression of class II histocompatibility antigens occurs in the absence of the invariant chain. J Exp Med. 1986 Nov 1;164(5):1490–1504. doi: 10.1084/jem.164.5.1490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tonnelle C., DeMars R., Long E. O. DO beta: a new beta chain gene in HLA-D with a distinct regulation of expression. EMBO J. 1985 Nov;4(11):2839–2847. doi: 10.1002/j.1460-2075.1985.tb04012.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Townsend A. R., Gotch F. M., Davey J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell. 1985 Sep;42(2):457–467. doi: 10.1016/0092-8674(85)90103-5. [DOI] [PubMed] [Google Scholar]
  33. Townsend A. R., McMichael A. J., Carter N. P., Huddleston J. A., Brownlee G. G. Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells. Cell. 1984 Nov;39(1):13–25. doi: 10.1016/0092-8674(84)90187-9. [DOI] [PubMed] [Google Scholar]
  34. Townsend A. R. Recognition of influenza virus proteins by cytotoxic T lymphocytes. Immunol Res. 1987;6(1-2):80–100. doi: 10.1007/BF02918106. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Yasukawa M., Zarling J. M. Human cytotoxic T cell clones directed against herpes simplex virus-infected cells. I. Lysis restricted by HLA class II MB and DR antigens. J Immunol. 1984 Jul;133(1):422–427. [PubMed] [Google Scholar]
  37. Yates J. L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. 1985 Feb 28-Mar 6Nature. 313(6005):812–815. doi: 10.1038/313812a0. [DOI] [PubMed] [Google Scholar]
  38. Yewdell J. W., Bennink J. R., Hosaka Y. Cells process exogenous proteins for recognition by cytotoxic T lymphocytes. Science. 1988 Feb 5;239(4840):637–640. doi: 10.1126/science.3257585. [DOI] [PubMed] [Google Scholar]
  39. Yewdell J. W., Bennink J. R., Smith G. L., Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1785–1789. doi: 10.1073/pnas.82.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

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