1887

Abstract

Cathepsin D and cathepsin B are endosomal/lysosomal proteases that are thought to play a role during antigen processing, releasing fragments for binding to major histocompatibility complex class II products and subsequent presentation to T cells. Here we treated purified foot-and-mouth disease virus (FMDV) strain AHolland with both enzymes. Cathepsin D, but not cathepsin B, was shown to release fragments from reduced or non-reduced FMDV under mild conditions . Twenty-eight predominant cathepsin D-released fragments were purified by HPLC and identified by amino acid composition analysis and sequencing. The unseparated set of fragments produced (the digest) was able to stimulate T cells from eight vaccinated cattle. With respect to the response to intact virus the extent of the response to the digest differed between animals: four animals could be classified as good responders, three as intermediate responders and one as a low responder. Subsequently, we investigated the proliferative T cell response to a large set of synthetic peptides in detail for two animals, one belonging to the group of good responders, the other being the low responder. The peptides covered all 28 cathepsin D-released fragments analysed and also several sequences not recovered from the digest. In this way seven T cell sites could be identified, five of which coincided with cathepsin D-released fragments. The other two T cell sites were VP2[54–72], being a homologue of a T cell site identified for FMDV strain OK and the N terminus of VP4. Whether the most dominantly recognized T cell site was recovered from the digest or not was shown to be related to the good or low response to the digest. These findings suggest a role for cathepsin D in the release of some but not all T cell-stimulatory fragments from FMDV.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-11-2937
1994-11-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/11/JV0750112937.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-11-2937&mimeType=html&fmt=ahah

References

  1. Acharya R., Fry E., Stuart D., Fox G., Rowlands D., Brown F. 1989; The three-dimensional structure of foot-and-mouth disease virus at 2·9 Å resolution. Nature; London: 337709–716
    [Google Scholar]
  2. Adorini L., Guery J. -C., Fuchs S., Ortiz-Navarrete V., Hammerling G. J., Momburg F. 1993; Processing of endogenously synthesized hen egg-white lysoszyme retained in the endoplasmic reticulum or in secretory form gives rise to a similar but not identical set of epitopes recognized by class II-restricted T cells. The Journal of Immunology 151:3576–3586
    [Google Scholar]
  3. Bahnemann H. G. 1975; Binary ethyleneimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production. Archives of Virology 47:47–56
    [Google Scholar]
  4. Bennett K., Levine T., Ellis J. S., Peanasky R. J., Samloff I. M., Kay J., Chain B. M. 1992; Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E. European Journal of Immunology 22:1519–1524
    [Google Scholar]
  5. Bond J. S., Barrett A. T. 1980; Degradation of fructose-1,6-biphosphate aldolase by cathepsin B. A further example of peptidyl dipeptidase activity of this protease. Biochemical Journal 189:17–25
    [Google Scholar]
  6. Brodsky F. M., Guagliardi L. E. 1991; The cell biology of antigen processing and presentation. Annual Review of Immunology 9:707–744
    [Google Scholar]
  7. Collen T. 1991 T cell responses of cattle to foot-and-mouth disease virus Ph.D. thesis University of London:
    [Google Scholar]
  8. Collins D. S., Unanue E. R., Harding C. 1991; Reduction of disulfide bonds within lysosomes is a key step in antigen processing. Journal of Immunology 147:4054–4059
    [Google Scholar]
  9. Davidson H. W., West M. A., Watts C. 1990; Endocytosis, intracellular trafficking, and processing of membrane IgG and monovalent antigen/membrane IgG complexes in B lymphocytes. Journal of Immunology 144:4101–4109
    [Google Scholar]
  10. Davies C. J., Joosten j., Andersson L., Arriens M. A., Bernoco D., Byrns G., Bissumbhar B., Vaneijk M. J. T., Ellegren H., Kristensen B., Lewin H. A., Morgan A. L. G., Muggli-Cockett N. E., Nilsson P. H. R., Oliver R. A., Park C. A., Vanderpoel J. J., Polli M., Spooner R. L., Stewart J. A. 1994; Polymorphism of bovine MHC class II genes. Joint report of the Fifth International Bovine Lymphocyte Antigen (BoLA) Workshop, Interlaken; Switzerland:1August 1992 European Journal of Immunogenetics 21 in press
    [Google Scholar]
  11. Denagel D. C., Pierce S. K. 1992; A case for chaperones in antigen processing. Immunology Today 13:87–89
    [Google Scholar]
  12. Diment S. 1990; Different roles for thiol and aspartyl proteases in antigen presentation of ovalbumin. Journal of Immunology 145:417–422
    [Google Scholar]
  13. Diment S., Stahl P. D. 1985; Macrophage endosomes contain proteases which degrade endocytosed protein ligands. Journal of Biological Chemistry 260:15311–15317
    [Google Scholar]
  14. Francis M. J., Fry C. M., Rowlands D. J., Bittle J. L., Houghten R. A., Lerner R. A., Brown F. 1987; Immune response to uncoupled peptides of foot-and-mouth disease virus. Immunology 61:1–6
    [Google Scholar]
  15. Glass E. J., Oliver R. A., Collen T., Doel T, Dimarchi R., Spooner R. L. 1991; MHC class II restricted recognition of FMDV peptides by bovine T-cells. Immunology 74:594–599
    [Google Scholar]
  16. Guagliardi L. E., Koppelman B., Blum J. S., Marks M. S., Cresswell P., Brodsky F. M. 1990; Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment. Nature; London: 343133–139
    [Google Scholar]
  17. Harding C. V., Geuze H. J. 1992; Class II MHC molecules are present in macrophage lysosomes and phagolysosomes that function in the phagocytic processing of Listeria monocytogenes for presentation to T-cells. Journal of Cellular Biology 119:531–542
    [Google Scholar]
  18. Harding C. V., Collins D. S., Slot J. W., Geuze H. J., Unanue E. R. 1991; Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T-cells. Cell 64:393–401
    [Google Scholar]
  19. Joosten I., Sanders M. F., Van Der Poel A., Williams J. L., Hepkema B. G., Hensen E. J. 1989; Biochemically defined polymorphism of bovine MHC class II antigens. Immunogenetics 29:213–216
    [Google Scholar]
  20. Mccoy K. L., Noone M., Inman J. K., Stutzman R. 1993; Exogenous antigens internalized through transferrin receptors activate CD4+ T-cells. Journal of Immunology 150:1691–1704
    [Google Scholar]
  21. Marsh E. W., Dalke D. P., Pierce S. K. 1992; Biochemical evidence for the rapid assembly and disassembly of processed antigen-major histocompatibility complex class II complexes in acidic vesicles of B cells. Journal of Experimental Medicine 175:425–436
    [Google Scholar]
  22. Meloen R. H., Briaire J. 1980; A study of the cross-reacting antigens on the intact foot-and-mouth disease virus and its 12S subunits with antisera against the structural proteins. Journal of General Virology 51:107–116
    [Google Scholar]
  23. Mouritsen S., Meldal M., Werdelin O., Stryhn Hansen A., Buus S. 1992; MHC molecules protect T-cell epitopes against proteolytic destruction. Journal of Immunology 149:1987–1993
    [Google Scholar]
  24. Peters P. J., Neefjes J. J., Oorschot V., Ploegh H. L., Geuze H. J. 1991; Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature; London: 349669–676
    [Google Scholar]
  25. Pfaff E., Mussgay M., Bohm H. O., Schulz G. E., Schaller H. 1982; Antibodies against a preselected peptide recognize and neutralize foot-and-mouth disease virus. EMBO Journal 1:869–874
    [Google Scholar]
  26. Puri J., Factorovitch Y. 1988; Selective inhibition of antigen presentation to cloned T cells by protease inhibitors. Journal of Immunology 141:3313–3317
    [Google Scholar]
  27. Rodriguez G. M., Diment S. 1992; Role of cathepsin D in antigen presentation of ovalbumin. Journal of Immunology 149:2894–2898
    [Google Scholar]
  28. Schwartz R. H. 1985; T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annual Review of Immunology 3:237–261
    [Google Scholar]
  29. Strohmaier K., Franze R., Adam K. -H. 1982; Location and characterization of the antigenic portion of the FMDV immunizing protein. Journal of General Virology 59:295–306
    [Google Scholar]
  30. Thomas A. A. M., Woortmeijer R. J., Puyk W., Barteling S. J. 1988; Antigenic sites on foot and mouth disease virus type A10. Journal of Virology 62:2782–2789
    [Google Scholar]
  31. Van Der Zee R., Wauben M. H. H., Lots T. H. A., Van Eden W. 1992; Simultaneous multiple peptide synthesis (SMPS) for the analysis of T cell epitopes. Journal of Cellular Biochemistry 16D:83
    [Google Scholar]
  32. Van Lierop M. J. C., Van Maanen K., Meloen R. H., Rutten V. P. M. G., Dejong W. A. C., Hensen E. J. 1992; Proliferative lymphocyte responses to foot-and-mouth disease virus and three FMDV peptides after vaccination or immunization with these peptides in cattle. Immunology 75:406–413
    [Google Scholar]
  33. Van Noort J. M., Van Der Drift A. C. M. 1989; The selectivity of cathepsin D suggests an involvement of the enzyme in the generation of T-cell epitopes. Journal of Biological Chemistry 264:14159–14164
    [Google Scholar]
  34. Van Noort J. M., Boon J., Van Der Drift A. C. M., Wagenaar J. P. A., Boots A. M. H., Boog C. J. P. 1991; Antigen processing by endosomal proteases determines which sites of sperm-whale myoglobin are eventually recognized by T-cells. European Journal of Immunology 21:1989–1996
    [Google Scholar]
  35. Vidard L., Rock K. L., Benacerraf B. 1991; The generation of immunogenic peptides can be selectively increased or decreased by proteolytic enzyme inhibitors. Journal of Immunology 147:1786–1791
    [Google Scholar]
  36. Vidard L., Rock K. L., Benacerraf B. 1992; Diversity in MHC class II ovalbumin T-cell epitopes generated by distinct proteases. Journal of Immunology 149:498–504
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-11-2937
Loading
/content/journal/jgv/10.1099/0022-1317-75-11-2937
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