1887

Abstract

AKR/Gross virus-specific cytotoxic T lymphocytes (CTL) from C57BL/6 (B6) mice are H-2K-restricted and recognize epitopes encoded by the prototype endogenous ecotropic murine leukaemia virus (Emv) AKR623. Four CTL epitopes have been identified by the use of synthetic peptides corresponding to AKR623-encoded amino acid sequences. Here we present both functional and nucleotide sequence data indicating that three closely related Emv share all of these CTL epitopes. We also found that one other murine leukaemia virus (MuLV) was not susceptible to lysis by these CTL. This is the ecotropic component of the LP-BM5 virus complex that causes murine AIDS. Nucleotide sequencing revealed that three of the four epitopes, including the immunodominant peptide, are altered in this virus. The other epitope was unchanged. These data implied that the inability of anti-AKR/Gross virus CTL to lyse cells infected with the LP-BM5 ecotropic (BM5eco) MuLV was due to the functional loss of three of the four CTL epitopes. Using recombinant vaccinia and Sindbis virus vectors, we have shown that the BM5eco-encoded form of the immunodominant epitope, which differs only by an arginine for lysine substitution at the N-terminal residue, fails to induce a CTL response in B6 mice. Immunization with BM5eco-infected cells also failed to induce MuLV-specific CTL. In light of the long passage history of the LP-BM5 complex in B6 mice, our results are consistent with a contribution of CTL-mediated immune selection to the evolution of the BM5eco MuLV.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-76-3-635
1995-03-01
2022-08-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/76/3/JV0760030635.html?itemId=/content/journal/jgv/10.1099/0022-1317-76-3-635&mimeType=html&fmt=ahah

References

  1. Aziz D., Hanna Z., Jolicoeur P. 1989; Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature 338:505–508
    [Google Scholar]
  2. Braciale T. J., Braciale V. L., Winkler M., Stroynowski I., Hood L., Sambrook J., Gething M.-J. 1987; 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. Journal of Experimental Medicine 166:678–692
    [Google Scholar]
  3. Chattopadhyay S., Sengupta D., Fredrickson T., Morse H., Hartley J. 1991; Characteristics and contributions of defective, ecotropic and mink cell focus-inducing viruses involved in a retrovirus-induced immunodeficiency syndrome of mice. Journal of Virology 65:4232–4241
    [Google Scholar]
  4. Copeland N., Bedigian H., Thomas C., Jenkins N. 1984; DNAs of two molecularly cloned endogenous ecotropic proviruses are poorly infectious in DNA transfection assays. Journal of Virology 49:437–444
    [Google Scholar]
  5. Coppola M. A., Green W. R. 1994; Cytotoxic T lymphocyte responses to the envelope proteins of endogenous ecotropic and mink cytopathic focus forming murine leukemia viruses in H-26 mice. Virology 202:500–505
    [Google Scholar]
  6. Falk K., Rotzschke O., Stevanovic S., Jung G., Ramensee H. 1991; Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290–296
    [Google Scholar]
  7. Green W. R. 1982; The in vitro generation of H-2-restricted cytotoxic T cells to AKR/Gross leukemia virus-induced tumors. I. Requirement for stimulation with allogeneic leukemia cells in vivo . Journal of Immunology 128:1043–1049
    [Google Scholar]
  8. Green W. R., Nowinski R., Henney C. 1979; The generation and specificity of cytotoxic T cells raised against syngeneic tumor cells bearing AKR/Gross murine leukemia virus antigens. Journal of Experimental Medicine 150:51–66
    [Google Scholar]
  9. Green W. R., Nowinski R., Henney C. 1980; Specificity of cytolytic T cells directed against AKR/Gross virus-induced syngeneic leukemias: antibodies directed against H-2K, but not against viral proteins, inhibit lysis. Journal of Immunology 125:647–655
    [Google Scholar]
  10. Green W. R., Graziano R. 1986; Cytolytic T lymphocyte-defined retroviral antigens on normal cells encoding by the Akv-1 proviral locus. Immunogene tics 23:106–110
    [Google Scholar]
  11. Hammond S. A., Bollinger R. C., Tobery T. W., Siliciano R. F. 1993; Transporter-independent processing of HIV-1 envelope protein for recognition by CD8+ T cells. Nature 364:158–161
    [Google Scholar]
  12. Henderson R. A., Michel H., Sakaguchi K., Shabanowitz J., Appella E., Hunt D. F., Engelhard V. H. 1992; HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science 255:1264–1266
    [Google Scholar]
  13. Herr W. 1984; Nucleotide sequence of AKV murine leukemia virus. Journal of Virology 49:471–478
    [Google Scholar]
  14. Jenkins N. A., Copeland N. G., Taylor B. A., Lee B. K. 1982; Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DNA in chromosomes of Mus musculus . Journal of Virology 43:26–36
    [Google Scholar]
  15. Jorgensen E. C., Kjeldgaard N. O., Pedersen F. S., Jorgensen P. 1988; A nucleotide substitution in the gag N-terminus of the endogenous ecotropic DBA/2 virus prevents Pr65gag myristilation and virus production. Journal of Virology 62:3217–3223
    [Google Scholar]
  16. Kelly M., Holland C. A., Lung M. L., Chattopadhyay S. K., Lowy D. R., Hopkins N. H. 1983; Nucleotide sequence of the 3′ end of MCF247 murine leukemia virus. Journal of Virology 45:291–298
    [Google Scholar]
  17. Latarjet R., Duplan J. F. 1962; Experiment and discussion on leukemogenesis by cell-free extracts of radiation-induced leukemia in mice. International Journal of Radiation Biology 5:223–233
    [Google Scholar]
  18. Lilly F., Duran-Reynals M. L., Rowe W. P. 1975; Correlation of early MuLV titer and H-2 type with spontaneous leukemia in mice of the BALB/cxAKR cross: a genetic analysis. Journal of Experimental Medicine 141:882–889
    [Google Scholar]
  19. Makino M., Morse H. C. M. III, Fredrickson T. N., Hartley J. W. 1990; H-2-associated and background genes influence the development of a murine retrovirus-induced immunodeficiency syndrome. Journal of Immunology 144:4347–4352
    [Google Scholar]
  20. Matsumura M., Fremont D. H., Peterson P. A., Wilson I. A. 1992; Emerging principles of the recognition of peptide antigens by MHC class I molecules. Science 257:927–934
    [Google Scholar]
  21. Monaco J. J. 1992; A molecular model of MHC class-I-restricted antigen processing. Immunology Today 13:173–179
    [Google Scholar]
  22. Plata F., Langlade-Demoyen P., Abastado J. P., Berbar T., Kourilsky P. 1987; Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo. Cell 48:231–240
    [Google Scholar]
  23. Schwarz D. A., Green W. R. 1994; CTL responses to the gag polyprotein encoded by the murine AIDS defective retrovirus are strain dependent. Journal of Immunology 153:436–441
    [Google Scholar]
  24. Sijts A. J. A. M., Ossendorp F., Mengede E. A. M., van den Elsen P. J., Melief C. J. M. 1994; Immunodominant mink cell focus-inducing murine leukemia virus (MuLV)-encoded CTL epitope, identified by its MHC class I-binding motif, explains MuLV-type specificity of MCF-directed cytotoxic T lymphocytes. Journal of Immunology 152:106–116
    [Google Scholar]
  25. Siracusa L., Russell L., Jenkins N., Copeland N. 1987; Allelic variation within the Emv-15 locus defines genomic sequences closely linked to the agouti locus on mouse chromosome 2. Genetics 117:85–92
    [Google Scholar]
  26. VanBleek G. M., Nathenson S. G. 1990; Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature 348:213–216
    [Google Scholar]
  27. White H. D., Robbins M. R., Green W. R. 1990; Mechanism of escape of endogenous murine leukemia virus Emv-14 from recognition by anti-AKR/Gross virus cytolytic T lymphocytes. Journal of Virology 64:2608–2619
    [Google Scholar]
  28. White H. D., Roeder D. A., Green W. R. 1994a; An immunodominant Kb-restricted peptide from the pl5E transmembrane protein of endogenous ecotropic murine leukemia virus (MuLV). AKR623 that restores susceptibility of a tumor line to anti-AKR/Gross MuLV cytotoxic T lymphocytes. Journal of Virology 68:897–904
    [Google Scholar]
  29. White H. D., Roeder D. A., Lam T., Green W. R. 1994b; Major and minor K^-restricted epitopes encoded by the endogenous ecotropic murine leukemia virus AKR623 that are recognized by anti-AKR/Gross MuLV CTL. Viral Immunology 7:51–59
    [Google Scholar]
  30. Yetter R. A., Buller R., Lee J. S., Elkins K., Mosier D. E., Fredrickson T. N., Morse H. C. 1988; CD4+ T cells are required for the development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS). Journal of Experimental Medicine 168:623–635
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-76-3-635
Loading
/content/journal/jgv/10.1099/0022-1317-76-3-635
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error