1887

Abstract

The majority of neurons in herpes simplex virus (HSV)-infected murine sensory ganglia are transiently induced to express MHC-I antigens at the cell surface, whereas only a minority are themselves productively infected. The aim of the current work was to determine whether MHC-I antigens can be expressed on the surfaces of infected neurons in addition to their uninfected neighbours. To address this aim a recombinant HSV type 1 strain, S-130, was used to deliver a mouse H2K gene, under control of the HCMV IE-1 promoter/enhancer, into human neuroblastoma cells and mouse primary sensory neurons . S-130 expressed H2K antigens on the surfaces of IMR-32 cells, a human neuroblastoma cell line that expresses very low levels of MHC-I constitutively. In K562 cells, which do not express MHC-I constitutively, H2K and β-microglobulin (βm) were shown to be co-expressed at the cell surface following S-130 infection. This observation was taken as evidence that class I heavy chain (αC) molecules encoded by the expression cassette in the HSV genome were transported to the cell surface as stable complexes with βm. Significantly, after introduction of S-130 into flank skin, H2K antigens were detected on the surfaces of primary sensory neurons in ganglia innervating the inoculation site. Our data show that HSV-infected murine primary sensory neurons and human neuroblastoma cells are capable of expressing cell-surface MHC-I molecules encoded by a transgene. From this, we infer that up-regulation of αC expression is, in principle, sufficient to overcome potential impediments to neuronal cell surface expression of MHC-I complexes.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-10-2375
2000-10-01
2019-10-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/10/0812375a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-10-2375&mimeType=html&fmt=ahah

References

  1. Allen, H., Fraser, J., Flyer, D., Calvin, S. & Flavell, R. ( 1986; ). Beta 2-microglobulin is not required for cell surface expression of the murine class I histocompatibility antigen H-2Db or of a truncated H-2Db. Proceedings of the National Academy of Sciences, USA 83, 7447-7451.[CrossRef]
    [Google Scholar]
  2. Bix, M. & Raulet, D. ( 1992; ). Functionally conformed free class I heavy chains exist on the surface of beta 2 microglobulin negative cells. Journal of Experimental Medicine 176, 829-834.[CrossRef]
    [Google Scholar]
  3. Chen, E., Karr, R. W., Frost, J. P., Gonwa, T. A. & Ginder, G. D. ( 1986; ). Gamma interferon and 5-azacytidine cause transcriptional elevation of class I major histocompatibility complex gene expression in K562 leukemia cells in the absence of differentiation. Molecular and Cellular Biology 6, 1698-1705.
    [Google Scholar]
  4. Degen, E., Cohen-Doyle, M. F. & Williams, D. B. ( 1992; ). Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both beta 2- microglobulin and peptide. Journal of Experimental Medicine 175, 1653-1661.[CrossRef]
    [Google Scholar]
  5. Eneroth, A., Kristensson, K., Ljungdahl, A. & Olsson, T. ( 1991; ). Interferon-gamma-like immunoreactivity in developing rat spinal ganglia neurons in vivo and in vitro. Journal of Neurocytology 20, 225-231.[CrossRef]
    [Google Scholar]
  6. Fruh, K., Ahn, K., Djaballah, H., Sempe, P., van Endert, P. M., Tampe, R., Peterson, P. A. & Yang, Y. ( 1995; ). A viral inhibitor of peptide transporters for antigen presentation. Nature 375, 415-418.[CrossRef]
    [Google Scholar]
  7. Goding, J. W. (1976). Monoclonal Antibodies: Principles and Practice, 2nd edn, pp. 87–88. London: Academic Press.
  8. Goldsmith, K., Chen, W., Johnson, D. C. & Hendricks, R. L. ( 1998; ). Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. Journal of Experimental Medicine 187, 341-348.[CrossRef]
    [Google Scholar]
  9. Hansen, T. H., Myers, N. B. & Lee, D. R. ( 1988; ). Studies of two antigenic forms of Ld with disparate beta 2-microglobulin (beta 2m) associations suggest that beta 2m facilitate the folding of the alpha 1 and alpha 2 domains during de novo synthesis. Journal of Immunology 140, 3522-3527.
    [Google Scholar]
  10. Hill, T. J., Field, H. J. & Blyth, W. A. ( 1975; ). Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. Journal of General Virology 28, 341-353.[CrossRef]
    [Google Scholar]
  11. Hill, A. B., Barnett, B. C., McMichael, A. J. & McGeoch, D. J. ( 1994; ). HLA class I molecules are not transported to the cell surface in cells infected with herpes simplex virus types 1 and 2. Journal of Immunology 152, 2736-2741.
    [Google Scholar]
  12. Hill, A., Jugovic, P., York, I., Russ, G., Bennink, J., Yewdell, J., Ploegh, H. & Johnson, D. ( 1995; ). Herpes simplex virus turns off the TAP to evade host immunity. Nature 375, 411-415.[CrossRef]
    [Google Scholar]
  13. Ho, D. Y. & Mocarski, E. S. ( 1989; ). Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proceedings of the National Academy of Sciences, USA 86, 7596-7600.[CrossRef]
    [Google Scholar]
  14. Jackson, M. R., Cohen-Doyle, M. F., Peterson, P. A. & Williams, D. B. ( 1994; ). Regulation of MHC class I transport by the molecular chaperone, calnexin (p88, IP90). Science 263, 384-387.[CrossRef]
    [Google Scholar]
  15. Joly, E. & Oldstone, M. B. ( 1992; ). Neuronal cells are deficient in loading peptides onto MHC class I molecules. Neuron 8, 1185-1190.[CrossRef]
    [Google Scholar]
  16. Joly, E., Mucke, L. & Oldstone, M. B. ( 1991; ). Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science 253, 1283-1285.[CrossRef]
    [Google Scholar]
  17. Kiefer, R. & Kreutzberg, G. W. ( 1990; ). Gamma interferon-like immunoreactivity in the rat nervous system. Neuroscience 37, 725-734.[CrossRef]
    [Google Scholar]
  18. Koelle, D. M., Tigges, M. A., Burke, R. L., Symington, F. W., Riddell, S. R., Abbo, H. & Corey, L. ( 1993; ). Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8+ cytotoxic T lymphocytes. Journal of Clinical Investigation 91, 961-968.[CrossRef]
    [Google Scholar]
  19. Lachmann, R. H. & Efstathiou, S. ( 1997; ). Utilization of the herpes simplex virus type 1 latency-associated regulatory region to drive stable reporter gene expression in the nervous system. Journal of Virology 71, 3197-3207.
    [Google Scholar]
  20. Lachmann, R. H., Brown, C. & Efstathiou, S. ( 1996; ). A murine RNA polymerase I promoter inserted into the herpes simplex virus type I genome is functional during lytic, but not latent infection. Journal of General Virology 77, 2575-2582.[CrossRef]
    [Google Scholar]
  21. Lalanne, J. L., Delarbre, C., Gachelin, G. & Kourilsky, P. ( 1983; ). A cDNA clone containing the entire coding sequence of a mouse H-2Kd histocompatibility antigen. Nucleic Acids Research 11, 1567-1577.[CrossRef]
    [Google Scholar]
  22. Lampson, L. A. & Fisher, C. A. ( 1984; ). Weak HLA and beta 2-microglobulin expression of neuronal cell lines can be modulated by interferon. Proceedings of the National Academy of Sciences, USA 81, 6476-6480.[CrossRef]
    [Google Scholar]
  23. Lozzio, B. B. & Lozzio, C. B. ( 1979; ). Properties and usefulness of the original K-562 human myelogenous leukemia cell line. Leukemia Research 3, 363-370.[CrossRef]
    [Google Scholar]
  24. Main, E. K., Monos, D. S. & Lampson, L. A. ( 1988; ). IFN-treated neuroblastoma cell lines remain resistant to T cell- mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity. Journal of Immunology 141, 2943-2950.
    [Google Scholar]
  25. Marozzi, A., Meneveri, R., Bunone, G., De Santis, C., Lopalco, L., Beretta, A., Agresti, A., Siccardi, A. G., Della Valle, G. & Ginelli, E. ( 1993; ). Expression of beta 2m-free HLA class I heavy chains in neuroblastoma cell lines. Scandinavian Journal of Immunology 37, 661-667.[CrossRef]
    [Google Scholar]
  26. Marrack, P. & Kappler, J. ( 1987; ). The T cell receptor. Science 238, 1073-1079.[CrossRef]
    [Google Scholar]
  27. Monaco, J. J. ( 1992; ). Genes in the MHC that may affect antigen processing. Current Opinion in Immunology 4, 70-73.[CrossRef]
    [Google Scholar]
  28. Moriarty, G. C., Moriarty, C. M. & Sternberger, L. A. ( 1973; ). Ultrastructural immunocytochemistry with unlabeled antibodies and the peroxidase–antiperoxidase complex. A technique more sensitive than radioimmunoassay. Journal of Histochemistry and Cytochemistry 21, 825-833.[CrossRef]
    [Google Scholar]
  29. Neefjes, J. J., Smit, L., Gehrmann, M. & Ploegh, H. L. ( 1992; ). The fate of the three subunits of major histocompatibility complex class I molecules. European Journal of Immunology 22, 1609-1614.[CrossRef]
    [Google Scholar]
  30. Neumann, H., Schmidt, H., Wilharm, E., Behrens, L. & Wekerle, H. ( 1997; ). Interferon gamma gene expression in sensory neurons: evidence for autocrine gene regulation. Journal of Experimental Medicine 186, 2023-2031.[CrossRef]
    [Google Scholar]
  31. O’Connor, C. G. & Ashman, L. K. ( 1982; ). Application of the nitrocellulose transfer technique and alkaline phosphatase conjugated anti-immunoglobulin for determination of the specificity of monoclonal antibodies to protein mixtures. Journal of Immunological Methods 54, 267-271.[CrossRef]
    [Google Scholar]
  32. Olsson, T., Kelic, S., Edlund, C., Bakhiet, M., Hojeberg, B., van der Meide, P. H., Ljungdahl, A. & Kristensson, K. ( 1994; ). Neuronal interferon-gamma immunoreactive molecule: bioactivities and purification. European Journal of Immunology 24, 308-314.[CrossRef]
    [Google Scholar]
  33. Ortiz-Navarrete, V. & Hammerling, G. J. ( 1991; ). Surface appearance and instability of empty H-2 class I molecules under physiological conditions. Proceedings of the National Academy of Sciences, USA 88, 3594-3597.[CrossRef]
    [Google Scholar]
  34. Parish, C. R. & McKenzie, I. F. ( 1978; ). A sensitive rosetting method for detecting subpopulations of lymphocytes which react with alloantisera. Journal of Immunological Methods 20, 173-183.[CrossRef]
    [Google Scholar]
  35. Pereira, R. A. & Simmons, A. ( 1999; ). Cell surface expression of H2 antigens on primary sensory neurons in response to acute but not latent herpes simplex virus infection in vivo. Journal of Virology 73, 6484-6489.
    [Google Scholar]
  36. Pereira, R. A., Tscharke, D. C. & Simmons, A. ( 1994; ). Upregulation of class I major histocompatibility complex gene expression in primary sensory neurons, satellite cells, and Schwann cells of mice in response to acute but not latent herpes simplex virus infection in vivo. Journal of Experimental Medicine 180, 841-850.[CrossRef]
    [Google Scholar]
  37. Posavad, C. M. & Rosenthal, K. L. ( 1992; ). Herpes simplex virus-infected human fibroblasts are resistant to and inhibit cytotoxic T-lymphocyte activity. Journal of Virology 66, 6264-6272.
    [Google Scholar]
  38. Rajagopalan, S., Xu, Y. & Brenner, M. B. ( 1994; ). Retention of unassembled components of integral membrane proteins by calnexin. Science 263, 387-390.[CrossRef]
    [Google Scholar]
  39. Russell, W. C. ( 1962; ). A sensitive and precise assay for herpes virus. Nature 195, 1028-1029.[CrossRef]
    [Google Scholar]
  40. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  41. Sandrin, M. S., Potter, T. A., Morgan, G. M. & McKenzie, I. F. ( 1978; ). Detection of mouse alloantibodies by rosetting with protein A-coated sheep red blood cells. Transplantation 26, 126-130.[CrossRef]
    [Google Scholar]
  42. Simmons, A. & Nash, A. A. ( 1984; ). Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease. Journal of Virology 52, 816-821.
    [Google Scholar]
  43. Simmons, A. & Tscharke, D. C. ( 1992; ). Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. Journal of Experimental Medicine 175, 1337-1344.[CrossRef]
    [Google Scholar]
  44. Stoppini, M., Bellotti, V., Mangione, P., Merlini, G. & Ferri, G. ( 1997; ). Use of anti-(beta2 microglobulin) mAb to study formation of amyloid fibrils. European Journal of Biochemistry 249, 21-26.[CrossRef]
    [Google Scholar]
  45. Sutherland, J., Mannoni, P., Rosa, F., Huyat, D., Turner, A. R. & Fellous, M. ( 1985; ). Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate. Human Immunology 12, 65-73.[CrossRef]
    [Google Scholar]
  46. Townsend, A. & Trowsdale, J. ( 1993; ). The transporters associated with antigen presentation. Seminars in Cell Biology 4, 53-61.[CrossRef]
    [Google Scholar]
  47. Van Agthoven, A. J., Lemonnier, F. A., Kkourilsky, F. M. & Jordan, B. R. ( 1984; ). Transformation of LMTK cells with purified HLA class I genes. V. A determinant on beta 2- microglobulin is controlled by heavy chain in a mouse–human hybrid complex: a biochemical analysis. Molecular Immunology 21, 175-179.[CrossRef]
    [Google Scholar]
  48. York, I. A., Roop, C., Andrews, D. W., Riddell, S. R., Graham, F. L. & Johnson, D. C. ( 1994; ). A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77, 525-535.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-10-2375
Loading
/content/journal/jgv/10.1099/0022-1317-81-10-2375
Loading

Data & Media loading...

Most Cited This Month

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