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Heat shock proteins in immune response to cancer: The Fourth Paradigm

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Abstract

The involvement of heat shock proteins in immune response is categorized into four distinct paradigms. In the First Paradigm, HSP derived from foreign organisms act as classical foreign antigens, and they elicit immune response to the non-conserved HSP epitopes. The Second Paradigm refers to instances where the host responds to self HSP to which there is no central or peripheral tolerance. The Third Paradigm involves molecular mimicry, where cross-reactivity between an HSP and another protein leads to an immune response to the latter under conditions which elicit an immune response to the former, such as infection with a bacterium whose immunodominant antigen is an HSP. The Fourth Paradigm refers to situations where an HSP-antigen complex elicits an effective response to the antigen andnot to the HSP. Thus the HSP acts as a carrier for the antigenic peptide. The role of HSP in recognition by γδ T cells may also fall into this paradigm. In this article, the Fourth Paradigm is considered as a crucial element in the development of vaccines against cancers and infectious diseases, and is analyzed through the prism of the observed association of hsp70 species with antigenic peptides.

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References

  1. Barrios, C., Lussow, A. R., van Embden, J., Van der Zee, R., Rappuoli, R., Constantino, P., Louis, J. A., Lambert, P. H., and Del Giudice, G., Mycobacterial heat shock proteins as carrier molecules II: The use of the 70 kDa mycobacterial heat shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and BCG priming. Eur. J. Immun.22 (1992) 1365–1372.

    Article  CAS  Google Scholar 

  2. Behr, C., Sarthou, J. L., Rogier, C., Trape, J. F., Dat, M. H., Michel, J. C., Aribot, G., Dieye, A., Claverie, J. M., and Druihle, P., Antibodies and reactive T cells against the malaria heat-shock protein Pf72/HSP70-1 and derived peptides in individuals continuously exposed to Plasmodium falciparum. J. Immun.149 (1992) 3321–3330.

    Article  CAS  PubMed  Google Scholar 

  3. Blachere, N. E., Udono, H., Janetzki, S., Li Z., Heike, M., and Srivastava, P. K., Heat shock protein vaccines against cancer. J. Immunotherapy14 (1993) 352–356.

    Article  CAS  Google Scholar 

  4. Blander, S. J., and Horwitz, M., Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease. J. invest. Dermat. 91 (1993) 717–23.

    CAS  Google Scholar 

  5. Cossart, P., and Mengaud, J., Listeria monocytogenes. A model system for the molecular study of intracellular parasitism. Molec. Biol. Med.6 (1989) 463–474.

    CAS  PubMed  Google Scholar 

  6. Davenport, M. P., McKenzie, K. R., Basten, A., and Britton, W. J., The variable C-terminal region of the Mycobacterium leprae. 70-kilodalton heat shock protein is the target for humoral immune responses. Infect. Immun.60 (1992) 1170–1177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Del Guidice, G., Experientia50 (1994) 1061–1066.

    Article  Google Scholar 

  8. Ferrarini, M., Heltai, S., Zocchi, M. R., and Rugarli, C., Unusual expression and localization of heat shock proteins in human tumor cells. Int. J. Cancer51 (1992) 613–619.

    Article  CAS  PubMed  Google Scholar 

  9. Flynn, G. C., Chappell, T. G., and Rothman, J. E., Peptide binding and release by proteins implicated as catalysts of protein assembly. Science245 (1989) 385–390.

    Article  CAS  PubMed  Google Scholar 

  10. Fu, Y. X., Vollmer, B., Katalaradi, H., Heyborne, K., Reardon, C., Miles, C., O'Brien, R., and Born, W., Structural requirements for peptides that stimulate a sub-set of gamma delta T cells. J. Immun.152 (1994) 1578–1588.

    Article  CAS  PubMed  Google Scholar 

  11. Germain, R. N., MHC-dependent antigen processing and peptide presentation: Providing ligands for T lymphocyte activation. Cell76 (1994) 287–300.

    Article  CAS  PubMed  Google Scholar 

  12. Harboe, M., and Quayle, A. J., Heat shock proteins: friend and foe? Clin. expl. Immun.86 (1991) 2–5.

    Article  CAS  Google Scholar 

  13. Houghton, A. N., Cancer antigens: Immune recognition of self and altered self. J. expl. Med.180 (1994) 1–4.

    Article  CAS  Google Scholar 

  14. Jones, D. B., Coulson, A. F., and Duff, G. W., Sequence homologies between hsp60 and autoantigens. Immun. Today.14 (1993) 115–118.

    CAS  Google Scholar 

  15. Kellner, H., Wen, J., Wang, J., Raybourne, R. B., Williams, K. M., and Yu, D. T., Serum antibodies from patient with ankylosing spondylitis and Reiter's syndrome are reactive with HLA-B27 cells transfected with the Mycobacterium tuberculosis hsp60 gene. Infect. Immun.62 (1994) 484–491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Koga, T., Wand-Wurttenberger, A., De Bruyn, J., Munk, M. E., Schoel, B., and Kaufmann, S. H. E., T cells against a bacterial heat shock protein recognize stressed macrophages. Science245 (1989) 1112–1115.

    Article  CAS  PubMed  Google Scholar 

  17. Lamb, J. R., Ivanyi, J., Rees, A. D. M., Rothbard, J., Howland, K., Young, R. A., and Young, D. B., Mapping of T cells epitopes using recombinant antigens and synthetic peptides. EMBO J.6 (1987) 1245–1249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lamb, J. R., Bal, V., Mendez-Samperio, P., Mehlert, A. S. A., Rothbard, J., Jindal, S., Young, R. A., and Young, D. B., Stress proteins may provide a link between the immune response to infection and autoimmunity. Int. Immun.1 (1989) 191–196.

    Article  CAS  PubMed  Google Scholar 

  19. Li, Z., and Srivastava, P. K., Tumor Rejection Antigen Gp96/Grp94 is An ATPase: Implications for protein folding and antigen presentation. EMBO J.12 (1993) 3143–3151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li, Z., and Srivastava, P. K., Heat shock proteins and antigen processing, in: MHC Molecules: Structural and Functional Aspects. Eds. H.-G. Rammense and G. Hammerling. BIM Press94 (1994) 37–47.

  21. Lussow, A. R., Barrios, C., van Embden, J., Van der Zee, R., Verdini, A. S., Pessi, A., Louis, J.A., Lambert, P. H., and Del Giudice, G., Mycobacterial heat shock proteins as carrier molecules. Eur. J. Immun.21 (1991) 2297–2302.

    Article  CAS  Google Scholar 

  22. Maki, R. G., Old, L. J., and Srivastava, P. K., Human homologue of murine tumor rejection antigen Gp96: Analysis of regulatory and coding regions and relationship to stress-induced proteins. Proc. natl Acad. Sci. USA87 (1990) 5658–5662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Matthews, R. C., The 14th C. L. Oakley Lecture. Candida albicans HSP 90: link between protective and auto immunity. J. med. Microbiol.36 (1992) 367–370.

    Article  CAS  PubMed  Google Scholar 

  24. Multhoff, G., Bolzler, C., Meier, T., Wiesnet, M., and Issels, R. D., Cell surface expression of a heat inducible 72 kDa heat shock protein (hsp72) antigenic epitope on human tumor cells but not on normal cells, in: Biology of Heat Shock Proteins and Chaperones, p 330. Cold Spring Harbour Laboratory, Cold Spring Harbour

  25. Munk, M. E., Schoel, B., Modrow, S., Karr, R. W., Young, R. A., and Kaufmann, S. H. E., T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65 kDa heat shock protein. J. Immun.143 (1989) 2844–2849.

    Article  CAS  PubMed  Google Scholar 

  26. Mustafa, A. S., Lundin, K. E., and Oftung, F., Human T cells recognize mycobacterial heat shock proteins in the context of multiple HLA-DR molecules: studies with healthy subjects vaccinated with Mycobacterium bovis BCG and Mycobacterium leprae. Infect. Immun.61 (1993) 5294–5301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Nossal, G. J. V., Negative selection of lymphocytes. Cell76 (1994) 229–240.

    Article  CAS  PubMed  Google Scholar 

  28. O'Brien, R., Happ, M. P., Dallas, A., Cranfill, R., Hall, L., Lang, J., Fu, X.-Y., Kubo, R., and Born, W., Recognition of a single hsp60 epitope by an entire subset of γδ T lymphocytes. Immun. Rev.121 (1991) 155–170.

    Article  CAS  PubMed  Google Scholar 

  29. Ottenhoff, T. H. and De Vries, R. R., Antigen reactivity and autoreactivity: two sides of the cellular immune response induced by mycobacteria. Curr. Topics Microbiol. Immun.155 (1990) 111–21.

    CAS  Google Scholar 

  30. Ovary, Z., and Benacerraf, B., Immunological specificity of the secondary response with dinitrophenyleated proteins. Proc. Soc. expl Biol. Med.114 (1963) 72–76.

    Article  CAS  Google Scholar 

  31. Palladino, M. A., Srivastava, P. K., Oettgen, H. F., and DeLeo, A. B., Expression of a shared tumor-specific antigen by two chemically induced BALB/c sarcomas. I. Detection by a cloned cytotoxic T cell line. Cancer Res.47 (1987) 5074–5079.

    PubMed  Google Scholar 

  32. Pardoll, D. M., The new look of tumor antigen in the 90's. Nature369 (1994) 357–358.

    Article  CAS  PubMed  Google Scholar 

  33. Pervin, K., Childerstone, A., Shinnick, T., Mizushima, Y., van der Zee, R., Hasan, A., Vaughan, R., and Lehner, T., T cell epitope expression of mycobacterial and homologous human 65 kDa heat shock protein peptides in short term cell lines from patients with Behcet's disease. J. Immun.151 (1993) 2273–282.

    Article  CAS  PubMed  Google Scholar 

  34. Pierce, S. K., Experientia50 (1994) 1026–1030.

    Article  CAS  PubMed  Google Scholar 

  35. Raff, M., Role of thymus-derived lymphocytes in the secondary humoral immune response in mice. Nature226 (1970) 1257–1258.

    Article  CAS  PubMed  Google Scholar 

  36. Rambukkana, A., Yong, S., and Das, P. K., Identification of a novel B-cell epitope of restricted specificity on the hsp 65-kDa protein of Mycobacterium tuberculosis. FEMS Microbiol Immun.3 (1991) 39–45.

    Article  CAS  Google Scholar 

  37. Rambukkana, A., Das, P. K., Witkamp, L., Yong, S., Meinardi, M., and Bos, J. D., Antibodies to mycobacterial 65 kDa heat shock protein and other immunodominant antigens in patients with psoriasis. J. invest. Dermat.100 (1993) 87–92.

    Article  CAS  Google Scholar 

  38. Roop, R. M., Price, M. L., Dunn, B. E., Boyle, S. M., Sriranganathan, N., and Schurig, G. G., Molecular cloning and nucleotide sequence analysis of the gene encoding the immunoreactive Brucella abortus Hsp60 protein, BA6OK. Microb. Pathogenesis12 (1992) 47–62.

    Article  CAS  Google Scholar 

  39. Sciammas, R., Johnson, R. M., Sperling, A. I., Brady, W., Linsley, P. S., Spear, P. G., and Fitch, F. W., Unique antigen recognition by a herpesvirus-specific TCR-gd cell. J. Immun.152 (1994) 5392–5397.

    Article  CAS  PubMed  Google Scholar 

  40. Srivastava, P. K., Peptide-binding heat shock proteins in the endoplasmic reticulum: Role in immune response to cancer and in antigen presentation. Adv. Cancer Res.62 (1993) 153–177.

    Article  CAS  PubMed  Google Scholar 

  41. Srivastava, P. K., Heat shock proteins as chaperones of unique and shared antigenic epitopes of human cancers: A novel approach to vaccination, in: Stress Proteins in Medicine. Ed. W. van Eden and D. B. Young. Marcel Dekker, Inc., (1994) in press.

  42. Srivastava, P. K., and Das, M. R., Serologically unique surface antigen of a rat hepatoma is also its tumor-associated transplantation antigen. Int. J. Cancer33 (1984) 417–422.

    Article  CAS  PubMed  Google Scholar 

  43. Srivastava, P. K., and Maki, R. G., Stress-induced proteins in immune response to cancer. Curr. Topics Microbiol. Immun.167 (1991) 109–123.

    CAS  Google Scholar 

  44. Srivastava, P. K., and Old, L. J., Individually distinct antigens of chemically induced mouse tumors. Immun. Today9 (1988) 78–83.

    CAS  Google Scholar 

  45. Srivastava, P. K., DeLeo, A. B., and Old, L. J., Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc. natl Acad. Sci. USA83 (1986) 3407–3411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Srivastava, P. K., Udono, H., Blachere, N. E., and Li, Z., Heat shock proteins transfer peptides during antigen processing and CTL priming. Immunogenetics39 (1994) 93–98.

    Article  CAS  PubMed  Google Scholar 

  47. Tamura, Y., Tsuboi, N., Sato, N., and Kikuchi, K., 70 kDa heat shock cognate protein is a transformation associated antigen and a possible target for host's anti-tumor immunity. J. Immun.151 (1993) 5516–5524.

    Article  CAS  PubMed  Google Scholar 

  48. Udono, H., and Srivastava, P. K., Heat shock protein 70-associated peptides elicit specific cancer immunity. J. expl Med.178 (1993) 1391–1396.

    Article  CAS  Google Scholar 

  49. Udono, H., Srivastava, P. K., Relative immunogenicities of Heat Shock Proteins gp96, hsp90 and hsp70 against chemically induced tumors. J. Immun.152 (1994) 5398–5403.

    Article  CAS  PubMed  Google Scholar 

  50. Udono, H., Levey, D. L., and Srivastava, P. K., Definition of T cell sub-sets mediating tumor-specific immunogenicity of cognate heat shock protein gp96. Proc. natl Acad. Sci. USA91 (1994) 3077–3081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. van Eden, W., Holoshitz, J., Nevo, Z., Frenkel, A., and Cohen, I. R., Arthritis induced by a T lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteroglycans. Proc. natl Acad. Sci. USA82 (1985) 5064–5067.

    Google Scholar 

  52. van Schooten, W. C., Elferink, D. G., Van-Embden, J., Anderson, D. C., De Vries, R. R., and Anderson, C. D., DR3-restricted T cells from different HLA. DR3. positive individuals recognize the same peptide (amino acids 2–12) of the mycobacterial 65kDa heat-shock protein. Eur. J. Immun.19 (1989) 2075–2079.

    Article  Google Scholar 

  53. Wallace, G. R., Ball, A. E., MacFarlane, J., El Safi, S. H., Miles, M. A., and Kelly, J. M., Mapping of a visceral leishmaniasis, specific immunodominant B-cell epitope of Leishmania donovani Hsp70. Infect. Immun.60 (1992) 2688–2693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Witkin, S., Jeremias, J., Toth, M., and Ledger, W. J., Cell-mediated immune response to the recombinant 57 kDa heat shock protein of Chlamydia trachomatis in women with salpingitis. J. infect. Dis.167 (1993) 1379–1383.

    Article  CAS  PubMed  Google Scholar 

  55. Young, D. B., The immune response to mycobacterial heat shock proteins. Autoimmunity7 (1990) 237–244.

    Article  CAS  PubMed  Google Scholar 

  56. Young, R. A., Stress proteins and immunology. A. Rev. Immun.8 (1990) 401–420.

    Article  CAS  Google Scholar 

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  1. Department of Biological Sciences, Fordham University, 10458, Bronx, New York, USA

    P. K. Srivastava

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Srivastava, P.K. Heat shock proteins in immune response to cancer: The Fourth Paradigm. Experientia 50, 1054–1060 (1994). https://doi.org/10.1007/BF01923461

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