1887

Abstract

Summary

Studies in this laboratory have shown that long term simian virus 40 (SV40)-specific cytolytic T lymphocyte (CTL) cultures established from the spleens of high responder C57BL/6 (B6; H-2) mice exhibit a preference for the selection of H-2D-restricted CTL clones. In this study, we have investigated the basis for this selection. Limiting dilution cultures were established using responder cells from the popliteal lymph nodes and the spleens of B6 mice immunized subcutaneously in the hind footpads or via the intraperitoneal route, respectively, with syngeneic SV40-transformed cells expressing a full length (1 to 708 amino acid residues) SV40 large T antigen. The relative frequency of CTL precursors (CTLp) able to expand in the presence of SV40-transformed stimulator cells and interleukin 2 and exhibit lytic activity against H-2 cells expressing full length T antigen ranged from 1/1900 to 1/15000 in the popliteal lymph node and from 1/8000 to 1/55000 in the spleen. In these two experimental systems, CTLp restricted to H-2K were apparently present at higher frequency than H-2D-restricted CTLp. Furthermore, CTLp recognizing determinants within the amino-terminal or carboxy-terminal halves of T antigen were generated in approximately equal numbers. The relative affinity of SV40-specific CTL, assessed by inhibition with anti-Lyt 2 monoclonal antibody, indicated that CTL restricted to H-2D interacted with their target with greater affinity than CTL restricted to H-2K. These data suggest that the predominance of isolation of H-2D-restricted CTL clones from long term cultures may be a function of the relative affinity of this population as a whole, rather than due to the immunodominance of this subpopulation during the response to SV40 T antigen.

Keyword(s): CTL recognition , frequency and SV40
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-69-10-2493
1988-10-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/69/10/JV0690102493.html?itemId=/content/journal/jgv/10.1099/0022-1317-69-10-2493&mimeType=html&fmt=ahah

References

  1. ALLOUCHE M., OWEN J. A., DOHERTY P. C. 1982; Limit dilution analysis of weak influenza immune T cell responses associated with H-2Kb and H-2Db. Journal of Immunology 129:689–693
    [Google Scholar]
  2. ANDERSON R. W., TEVETHIA M. J., KALDERON D., SMITH A. E., TEVETHIA S. S. 1988; Fine mapping of two distinct antigenic sites on SV40 T antigen reactive with SV40-specific cytotoxic T cell clones using SV40 deletion mutants. Journal of Virology 62:285–296
    [Google Scholar]
  3. BODMER H. C, PEMBERTON R. M., ROTHBARD J. B., ASKONAS B. A. 1988; Enhanced recognition of a modified peptide antigen by cytotoxic T cells specific for influenza nucleoprotein. Cell 52:253–258
    [Google Scholar]
  4. BUTEL J. S., JARVIS D. L. 1986; The plasma-membrane-associated form of SV40 large tumor antigen: biochemical and biological properties. Biochimica et biophysica acta 865:171–197
    [Google Scholar]
  5. CAMPBELL A. E., FOLEY F. L., TEVETHIA S. S. 1983; Determination of multiple antigenic sites of the SV40 transplantation rejection antigen using cytotoxic T lymphocyte clones. Journal of Immunology 130:490–492
    [Google Scholar]
  6. DEPPERT W., HANKE K., HENNINGS R. 1980; Simian virus 40 T-antigen-related cell surface antigen: serological demonstration on simian virus 40-transformed monolayer cells in situ. Journal of Virology 35:505–518
    [Google Scholar]
  7. DIALYNIS D. P., WILDE D. B., MARRACK P., PIERRES A., WALL K. A., HARRAN W., OTTEN G., LOKEN M. R., PIERRES M., KAPPLER J., FITCH F. W. 1983; Characterization of the murine antigenic determinant, designated by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen reactivity. Immunological Reviews 74:29–56
    [Google Scholar]
  8. FLYER D. C, ANDERSON R. W., TEVETHIA S. S. 1982; Lyt phenotype of H-2b CTL effectors and precursors specific for the SV40 transplantation rejection antigen. Journal of Immunology 129:2368–2371
    [Google Scholar]
  9. GLORIOSO J., KEES V., KUMEL G., KIRCHNER N., KRAMMER P. H. 1985; Identification of herpes simplex virus type 1 (HSV-1) glycoprotein gC as the immunodominant antigen for HSV-1-specific memory cytotoxic T lymphocytes. Journal of Immunology 135:575–582
    [Google Scholar]
  10. GOODING L. R. 1977; Specificities of killing by cytotoxic lymphocytes generated in vivo and in vitro to syngeneic SV40 transformed cells. Journal of Immunology 118:920–927
    [Google Scholar]
  11. GOODING L. R. 1979a; Specificities of killing by T lymphocytes generated against syngeneic SV40-transformants: studies employing recombinants within the H-2 complex. Journal of Immunology 122:1002–1008
    [Google Scholar]
  12. GOODING L. R. 1979b; Antibody blockage of lysis by T lymphocyte effectors generated against SV40 transformed cells. Journal of Immunology 122:2328–2336
    [Google Scholar]
  13. GOODING L. R. 1980; Anomalous behavior of H-2Kb in immunity to syngeneic SV40 transformed cells: evidence for cytotoxic T cell recognition of H-2/SV40 membrane antigen complexes. Journal of Immunology 124:1612–1619
    [Google Scholar]
  14. GOODING L. R. 1982; Characterization of a progressive tumor from C3H fibroblasts transformed in vitro with SV40 virus. Immunoresistance in vivo correlates with phenotypic loss of H-2Kk. Journal of Immunology 129:1306–1312
    [Google Scholar]
  15. GOODING L. R., EDWARDS C. B. 1980; H-2 antigen requirements in the in vitro induction of SV40-specific cytotoxic T lymphocytes. Journal of Immunology 124:1258–1262
    [Google Scholar]
  16. GOODING L. R., O’CONNELL K. A. 1983; Recognition by cytotoxic T lymphocytes of cells expressing fragments of the SV40 tumor antigen. Journal of Immunology 131:2580–2586
    [Google Scholar]
  17. HABEL K., SILVERBERG R. J. 1960; Relationship of polyoma virus and tumor in vivo. Virology 12:463–476
    [Google Scholar]
  18. JENNINGS S. R., RICE P. L., PAN S., KNOWLES B. B., TEVETHIA S. S. 1984; Recognition of herpes simplex virus antigens on the surface of mouse cells of the H-2b haplotype by virus-specific cytotoxic T lymphocytes. Journal of Immunology 132:475–481
    [Google Scholar]
  19. KALDERON D., SMITH A. E. 1984; In vitro mutagenesis of a putative DNA binding domain of SV40 large T antigen. Virology 139:109–137
    [Google Scholar]
  20. KNOWLES B. B., KONCAR M., PFIZENMAIER K., SOLTER D., ADEN D. P., TRINCHIERI G. 1979; Genetic control of the cytotoxic T cell response to SV40 tumor-associated specific antigen. Journal of Immunology 122:1798–1806
    [Google Scholar]
  21. KOSZINOWSKI U. H., KIEL G. M., SCHWARZ H., SCHICKENDANZ J., REDDEHASE M. J. 1987; A nonstructural polypeptide encoded by immediate-early transcription unit 1 of murine cytomegalovirus is recognized by cytolytic T lymphocytes. Journal of Experimental Medicine 166:289–294
    [Google Scholar]
  22. LEFKOVITS I., WALDMANN H. 1979 Limiting Dilution Analysis of Cells in the Immune System38–59 Cambridge: Cambridge University Press;
    [Google Scholar]
  23. MACDONALD H. R., THIERNESSE N., CEROTTINI J.-C. 1981; Inhibition of T cell-mediated cytolysis by monoclonal antibodies directed against Lyt-2: heterogeneity of inhibition at the clonal level. Journal of Immunology 126:1671–1675
    [Google Scholar]
  24. MACDONALD H. R., GLASEBROOK A. L., BRON C, KELSO A., CEROTTINI J.-C. 1982; Clonal heterogeneity in the functional requirement for Lyt2/3 molecules on cytolytic T lymphocytes (CTL): possible implications for the affinity of CTL antigen receptors. Immunological Reviews 68:89–115
    [Google Scholar]
  25. O’CONNELL K. A., GOODING L. R. 1984; Cloned cytotoxic T cells recognize cells expressing discrete fragments of SV40 tumor antigen. Journal of Immunology 132:953–958
    [Google Scholar]
  26. PALA P., ASKONAS B. A. 1986; Low responder MHC alleles for Tc recognition of influenza nucleoprotein. Immunogenetics 23:279–284
    [Google Scholar]
  27. PAN S., KNOWLES B. B. 1983; Monoclonal antibodies to SV40 T antigen block lysis of cloned cytotoxic T-cell lines specific for SV40 TASA. Virology 125:1–7
    [Google Scholar]
  28. PFIZENMAIER K., TRINCHIERI G., SOLTER D. P., KNOWLES B. B. 1978; Mapping of H-2 genes associated with T cell-mediated cytotoxic responses to SV40 tumour-associated specific antigen. Nature, London 274:691–693
    [Google Scholar]
  29. PFIZENMAIER K., PAN S.-H., KNOWLES B. B. 1980; Preferential H-2 association in cytotoxic T cell responses to SV40 tumor-associated specific antigens. Journal of Immunology 124:1888–1891
    [Google Scholar]
  30. PRETELL J., GREENFIELD R. S., TEVETHIA S. S. 1979; Biology of the simian virus 40 (SV40) transplantation antigen (TrAg). V. In vitro demonstration of SV40 TrAg in SV40 infected nonpermissive mouse cells by lymphocyte-mediated cytotoxic assay. Virology 97:32–41
    [Google Scholar]
  31. RAULET D. H., GOTTLEIB P. D., BEVAN M. J. 1980; Fractionation of lymphocyte populations with monoclonal antibodies specific for Lyt 2.2 and Lyt 3.1. Journal of Immunology 125:1136–1143
    [Google Scholar]
  32. REDDEHASE M. J., COX J. H., KOSZINOWSKI V. H. 1982; Frequency analysis of cytolytic T cell precursors (CTLp) generated in vivo during lethal rabies infection of mice. I. Distinction of CTLp with different interleukin 2 sensitivity. European Journal of Immunology 12:519–523
    [Google Scholar]
  33. RIGBY P. W. J., LANE D. P. 1983; The structure and function of the simian virus 40 large T antigen. Advances in Viral Oncology 3:31–57
    [Google Scholar]
  34. ROUSE B. T., LARSEN H. S., WAGNER H. 1983; Frequency of cytotoxic T lymphocyte precursors to herpes simplex virus type 1 as determined by limiting dilution analysis. Infection and Immunity 39:785–792
    [Google Scholar]
  35. SANTOS M., BUTEL J. S. 1982a; Association of SV40 large tumor antigen and cellular proteins on the surface of SV40-transformed mouse cells. Journal of Virology 120:1–17
    [Google Scholar]
  36. SANTOS M., BUTEL J. S. 1982b; Detection of a complex of SV40 large tumor antigen and 53K cellular protein on the surface of transformed mouse cells. Journal of Cellular Biochemistry 19:127–144
    [Google Scholar]
  37. SARMIENTO M., GLASEBROOK A. L., FITCH F. W. 1980; IgM or IgG monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. Journal of Immunology 125:2665–2672
    [Google Scholar]
  38. SOÛLE H. R., BUTEL J. S. 1979; Subcellular localization of simian virus 40 large tumor antigen. Journal of Virology 30:523–532
    [Google Scholar]
  39. TANAKA Y., TEVETHIA S. S. 1988; In vitro selection of SV40 T antigen epitope loss variants by site specific cytotoxic T lymphocyte clones. Journal of Immunology 140:4348–4354
    [Google Scholar]
  40. TANAKA Y., TEVETHIA M. J., KALDERON D., SMITH A. E., TEVETHIA S. S. 1988; Clustering of antigenic sites recognized by cytotoxic T lymphocyte clones in the amino terminal half of SV40 T antigen. Virology 162:427–436
    [Google Scholar]
  41. TASWELL C. 1981; Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. Journal of Immunology 128:1614–1619
    [Google Scholar]
  42. TEGTMEYER P., SCHWARTZ M., COLLINS J. K., RUNDELL K. 1975; Regulation of tumor antigen synthesis by simian virus 40 gene A. Journal of Virology 16:168–178
    [Google Scholar]
  43. TENEN D. G., GAREWAL H., HAINES L. L., HUDSON I., WOODWARD V., LIGHT S., LIVINGSTON D. M. 1977; Purification of simian virus 40 tumor antigen from a line of simian virus 40-transformed human cells. Proceedings of the National Academy of Sciences, U.S.A 75:3745–3749
    [Google Scholar]
  44. TEVETHIA S. S., GREENFIELD R. S., FLYER D. C., TEVETHIA M. J. 1980; SV40 transplantation antigen: relationship to SV40-specific proteins. Cold Spring Harbor Symposia on Quantitative Biology 44:235–242
    [Google Scholar]
  45. TEVETHIA S. S., TEVETHIA M. J., LEWIS A. J., REDDY V. B., WEISSMAN S. M. 1983; Biology of simian virus 40 (SV40) transplantation antigen (TrAg). IX. Analysis of TrAg in mouse cells synthesizing truncated SV40 large T antigen. Virology 128:319–330
    [Google Scholar]
  46. TEVETHIA S. S., LEWIS A. J., CAMPBELL A. E., TEVETHIA M. J., RIGBY P. W. J. 1984; Simian virus 40 specific cytotoxic T lymphocyte clones localize two distinct TSTA sites on cells synthesizing a 48kD SV40 T antigen. Virology 133:443–447
    [Google Scholar]
  47. TOOZE J. 1980 Molecular biology of tumor viruses. DNA Tumor Viruses Edited by Tooze J. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  48. TOWNSEND A. R. M., ROTHBARD J., GOTCH F. M., BAHADUR G., WRAITH D., MCMICHAEL A. I. 1986; The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:959–968
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-69-10-2493
Loading
/content/journal/jgv/10.1099/0022-1317-69-10-2493
Loading

Data & Media loading...

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