Abstract
Heat shock proteins (HSPs) serve as molecular chaperones of polypeptides transported between cell organelles, and contribute to the folding of nascent and altered proteins. A rapidly growing body of data suggests that at least in mammals, the HSPs 70 and gp96, are involved in immunity (review in Srivastava et al., 1998). Considering some analogy between MHC molecules and HSPs, it has been hypothesized that HSPs may have been forerunner presenting molecules, and that this primitive antigen presenting mechanism was integrated in the newly evolved MHC system (Srivastava and Heike, 1991). Structural similarities between hsp70 and major histocompatibility complex (MHC) class I peptide binding sites led Flajnik (1991) to a partially similar suggestion. Three characteristics of HSPs are reminiscent of MHC molecules (Table 1). First, these HSPs can physiologically associate with a large variety of antigenic peptides derived from cellular proteins. Second, after immunization with HSP-peptide complexes, T-cell immune responses are elicited against the chaperoned peptide. Finally, under certain circumstances (cell surface expression, cell death), these intracellular proteins end up in the extracellular compartment. Given the high degree of structural conservation of HSPs during evolution, their possible involvement in immune function, in general, and tumor immunity in particular, may be reflective of an ancient origin of HSPs that was contemporary with, or even antecedent to, the emergence of the vertebrate adaptive immune system that uses MHC presentation and restriction. In this review, we will examine the extent to which those immunological properties of HSPs found in mammals (peptide binding and chaperoning, adjuvanticity, immunogenicity) are phylogenetically conserved, and by extension, whether HSPs may be an evolutionary bridge between innate and adaptive immunity.
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References
Agrawal, A., Eastamn, Q., and Schatz, D. (1998). Transposition mediated by Ragl and Rag2 and its implication for the evolution of the immune system. Nature 394: 744–751.
Altmeyer, A., Maki, R.G., Feldweg, A.M., Heike, M., Protopopov, V.P., Masur, S.K. and Srivastava, P. (1996). Tumor-specific cell surface expression of KDEL-containing, endoplasmic reticular heat shock protein gp96. Int. J. Cancer 69: 340–349.
Amato, R., Murray L., Wood, B., Savary, C., Tomasovic S., Srivastava P.K„ and Reitsma, D. (1999). ASCO meeting
Anderson, S.L., Shen, T., Lou, J., Xing, L., Blachere, N.E., Srivastava, P. and Rubin B.Y. (1994). The endoplasmic reticular heat shock protein gp96 is transcriptionally upregulated in interferon-treated cells. J. Exp. Med. 180: 1565–1569.
Arnold, D., Faath, S., Rammensee, H. and Shild H. (1995). Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96. J. Exp. Med. la 885–889.
Bartl, S. (1998). What sharks can tell us about the evolution of MHC genes. Immunol. Rev. 166: 317–331.
Basu, S., Suto, R., Binder, J. and Srivastava, P. (1998). Heat-shock proteins as novel mediators of cytokine secretion by macrophages. Cell Stress & Chaperones 3 (suppl. 1), 11.
Binder, J., Ménoret, A. and Srivastava, P. (1998). Receptor-dependent and receptor-independent representation of heat-shock protein-chaperoned peptides. Cell Stress & Chaperones 3 (suppl. 1), 2.
Blachere, N.E., Li, Z., Chandawarkar, R.Y., Suto, R., Jaikaria, N.S., Basu, S., Udono, H and Srivastava, P. K. (1997). Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J. Exp. Med. 1k: 1315–1322.
Ciupitu, A., Peterson, M., O’Donnell, C., Williams, K., Jindal, S., Kiessling, R., and Welsh, M. (1998). Immunization with a lymphocytic choriomeningitis virus peptide mixed with heat shock protein 70 results in protective antiviral immunity specific cytotoxic T lymphocytes. J. Exp. Med. 187: 685–691.
Clem, L.W., Bly, J. E., Wilson, M., Chinchar, V.G., Stuge, T., Barker, K., Luft, C., Rycyzyn, M., Hogan, R. J., van Lopik, T. and Miller, N. W. (1996). Fish immunology: The utility of immortalized lymphoid cells-a mini review. Vet. Immunol. Immunopath. 54: 137–144.
Cohen, N. 1968. Chronic skin graft rejection in the Urodela. I. A comparative study of the first-and second-set allograft reactions. J. Exp. Zool. 167:37–48.
Du Pasquier, L., and Flajnik, M. (1999). Origin and evolution of the vertebrate immune system. In Paul, W. E. ed., Fundamental Immunology, Fourth Edition p. 605–649. Raven Press New York.
Du Pasquier L. and Robert J. (1992). In vitro growth of thymic tumor cell lines from Xenopus. Devel. Immunol. 2: 295–307.
Du Pasquier, L., Schwager, J., and Flajnik, M. F. (1989). The immune system of Xenopus. Annu. Rev. Immunol. 7: 251–275.
Flajnik, M.F., Canel, C., Kramer, J., and Kasahara, M. (1991). Which came first, MHC class I or class II? Immunogenetics E: 295–300.
Flajnik, M., Kasahara, M., Shum, P., Salter-Cid, L., Taylor, A., and Du Pasquier L. (1993). A novel type of class I gene organization in vertebrates: a large family of non-MHC-linked class I genes is expressed at the RNA level in the amphibian Xenopus. EMBO J.12: 4385–4495.
Gupta, R. (1995). Phylogenetic analysis of the 90kK heat shock family of protein sequences and ab examination of the relationship among animals, plants, and fungi species. Mol. Biol. Evol. 12: 1063–1073.
Hendrick, J.P. and Hartl, F.U. (1993). Molecular chaperone functions of heat-shock proteins. Annu. Rev. Biochem. í82:349–375.
Hiom, K., Melek, M., and Gellert, M. (1998). DNA transposition by the RAG! and RAG2 proteins: a possible source of oncogenic translocation. Cell 24: 463–470.
Horton, T. L., Ritchie, P., Watson, M., and Horton, J. D. (1998). Natural cytotoxicity towards allogeneic tumour targets in Xenopus mediated by diverse splenocyte populations. Dev. Comp. Immunol. 22: 217–230.
Kim, H.T, Nelson, EL, Clayburger, C., Sanjanwala, M., Sklar, J. and Krensky, A.M. (1995). Gamma delta T cell recognition of tumor Ig peptide. J. Immunol. 154; 1614–1623.
Kobel, H.R. and Du Pasquier, L. (1977). Strains and species of Xenopus for immunological research. In: Developmental Immunology, Solomon, J.B. and Horton, J.D. Eds, (Amsterdam, ElsevierNorth-Holland), pp. 299–306.
Kock, G., Smith, M., Macer, D., Webster, P., and Mortara, R. (1986). Endoplasmic reticulum contains a common, abundant calcium-binding glycoprotein, endoplasmin.J. Cell. Sci. 86: 217–232.
Krone, P.H. and Sass, J. (1994). Hsp90a and hsp90b genes are present in the zebrafish and are differentially regulated in developing embryos. Biochem. Biophys. Res. Comm. 204: 746–752.
Lammert, E., Arnold, D., Nijenhuis, M., Momburg, F., Hammerliing, G., Brunner, J., Stevanovic, S., Rammensee, H. and Schild, H. (1997). The endoplasmic reticulum-resident stress protein gp96 binds peptides translocated by TAP. Eur. J. Immunol. 21: 923–927.
Lewis, J., Janestzki, S., Livingston, P., Desantis, D., Williams, L., Klitnstra, W., Reitman, D., Hougaton A., Srivastava, P., and Bronnan, J. (1999). ASCO meeting.
Marchalonis, J., Schluter, S., Bernstein, R. and Hohman, V. (1998). Antibodies of sharks: revolution and evolutions. Immunol. Rev. 166: 103–122.
Mayr, E. (1997). This is biology. The science of the living world. The Belknap press of Harvard University press. Cambridge MS. 323 pp.
Matzinger, P. (1994). Tolerance, danger, and the extended family. Ann. Rev. Immunol. 12: 991–1045.
Ménoret, A., Peng, P. and Srivastava, P.K. (1999). Association of peptides with the heat shock protein gp96 occurs in vivo and not post cell lysis. Bioch. Biophys.Res. Corn. (In press)
Moore, S.K., Kozak, C., Robinson, E.A., Ullrich, S.J. and Appella, E. (1989). Mutine 86- and 84-kDa heat shock proteins, cDNA sequences, chromosome assignments, and evolutionary origins. J. Biol. Chem. 264: 5343–5351.
Morimoto, E., Tissiere, A., and Georgopoulos, eds (1994). The biology of heat shock proteins and molecular chaperones. Cold Spring Harbor Laboratory, Cold Sprong Harbor, NY.
Multhoff, G., Botzler, C., Wiesnet, M., Müller, E., Meier, T., Wilmann, W., and Issels, R. (1995). A stress-inducible 72-kDa heat-shock protein (hsp72) is expressed on the surface of human tumor cells, but not on normal cells. Int. J. Cancer 61: 272.
Multhoff, G., Botzler, C., Jennen, L., Schmidt, J., Ellwart, J., and Issels, R. (1997). Heat shock protein 72 on tumor cells a recognition structure for natural killer cells. J. Immunol. 158: 4341–4350.
Nicchitta CV. (1998). Biochemical, cell biological and immunological issues surrounding the endoplasmic reticulum chaperone GRP94/gp96. Current Op. Immunol; 11 103–109.
Nieland, T.J.F., M.C.A. Tan, M. van Muijen, F. Koning, A. Kruisbeek, and G.M. van Bieck., (1996) Isolation of an immunodominant viral peptide that is enbdogenously bound to the stress protein gp96/grp94. Proc. Natl. Acad. Sci.(USA) 23: 6135–6139.
O’Brien, R., Happ, M., Dallas, A., Palmer, E., Kubo, R. and Born, W. (1989). Stimulation of a major subset of lymphocytes expressing T cell receptor gamma delta by an antigen derived from Mycobacterium tuberculosis. Cell 51: 667–674.
Parham, P. (1994). The rise and fall of great class I genes. Semin. Immunol. ¢: 373–382
Parham, P. Ed. (1998). Immune system of ectothermic vertebrates. Immunol. Rev. 166. 384 pp.
Robert, J. and Du Pasquier L. (1996). Xenopus lymphoid tumor cell lines. In: Manual of Immunological Methods ed. I. Lefkovitz. Academic Press, pp. 2367–237.
Robert, J., Guiet, C. and Du Pasquier L. (1994). Lymphoid tumors of Xenopus laevis with different capacities for growth in larvae and adults. Devel. Immunol. 3: 297–307.
Robert, J., Guiet, C. and Du Pasquier L. (1995). Ontogeny of the alloimmune response against transplanted tumor in Xenopus laevis. Differentiation 52: 135–144.
Robert, J., Guiet C., Cohen, N., and Du Pasquier L. (1997). Effects of thymectomy and tolerance induction on tumor immunity in adult Xenopus laevis. Internat. J. Canc. 70: 330–334.
Robert, J., Ménoret, A., Srivastava, P. and Cohen, N. 1998. The tumor-specific immunogenicity of the heat-shock protein gp96 is conserved during evolution. Cell Stress & Chaperones 3:suppl.1, 22.
Robert, J., and Cohen, N. (1998). Evolution of immune surveillance. Immunol. Rev. 166:231–243.
Robert, J., Ménoret, A., and Cohen, N. (1999). Cell surface expression of the endoplasmic reticular heat shock protein gp96 is phylogenetically conserved. J. Immunol. (In press).
Robert, J., Ménoret, A., Cohen N., and Srivastava, A. (1999). The immunological properties of the heat shock protein gp96 are conserved across phylogenetically distant species. (submitted).
Salter-Cid, L. and Flajnik, M. (1995). Evolution and developmental regulation of the major histocompatibility complex. Crit. Rev. Immunol. 35: 31–75.
Salter-Cid, L., Nonaka, M., and Flajnik, MF. (1998). Expression of MHC class Ia and class lb during ontogeny: high expression in epithelia and coregulation of class Ia and lmp7 genes. J. Inununol.: 2853–61
Sammut, B., Laurens, V., and Toumefier, A. (1997). Isolation of Mhc class I cDNAs from the axolotl Ambystoma mexicanum. Immunogenetics 45: 285–294.
Srivastava, P.K., Deleo, A., and Old, L.J. (1986). Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc. Natl. Acad. Sci. USA 83: 3407–3411.
Srivastava, P.K and Heike, M. (1991). Tumor-specific immunogenicity of stress-induced proteins: convergence of two evolutionary pathways of antigen presentation? Sem. Immunol. 3: 57–64.
Srivastava„ P.K and Maki, R.G. (1991). Stress-induced proteins in immune response to Cancer. Curr. Top. Microbiol. Immunol. 167: 109–121.
Srivastava, P.K., Udono, H., Blachere, N.E. and Li, Z. (1994). Heat shock proteins transfer peptides during antigen processing and CTL priming. Immunogenetics 39: 93–98.
Srivastava, P.K. (1997). Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens. Immunol. Methods Manual 9.11: 737–747.
Srivastava PK., Ménoret A., Basu S., Binder RJ., McQuade KL. 1998. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity. 8:657–65
Suto, R. and Srivastava, P.K. (1995). A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269: 1585–1588.
Tamura, Y., Tsuboi, N., Sato, N. and Kibuchi, K. (1993). 70-kDa heat-shock cognate protein is a transformation-associated antigen and a possible target for host’s anti-tumor immunity. J. Immunol. 151: 5516–5524.
Tamura, Y, Peng, P, Liu, K, Daou, M and Srivastava, P.K. (1997) Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 278: 117–119.
Takemoto, H., Yoshimori, T., Yamamoto, A., Myiata, Y., Yahara, I., Inoue, K., and Tashiro, Y. (1992). Heavy chain binding protein (BiP/GRP78) and endoplasmin are exported from the endoplasmic reticulum in rat exocrine pancreatic cells, similar to protein disulfide-isomerase. Arch. Biochem. Biophysics 296: 129–134.
Udono, H. and Srivastava, P.K. (1993). Heat shock protein 70-associated peptides elicit specific cancer immunity. J. Exp. Med. 178: 1391–1396.
Udono, H. and Srivastava, P.K. (1994). Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90 and hsp70. J. Immunol. 5: 5398–5403.
Udono, H., Levey, D.L. and Srivastava, P.K. (1994). Cellular requirements for tumor-specific immunity elicited by heat shock proteins: tumor rejection antigen gp96 primes CD8’ T cells in vivo. Proc. Natl. Acad. Sci. USA 21: 3077–3081.
Ullrich, S., Robinson, A., Law, W., Willingham, M., and Appella E. (1986). A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proc. Natl. Acad. Sci. USA 83: 3121–3128.
Van Buskirk, A., Crump, B., Margoliash, E. and Pierce, S. (1989). A peptide-binding protein having a role in antigen presentation is a member of the hsp70 family. J. Exp. Med. ID: 1799–1809.
Wassenberg, J., Dezfulian, C., and Nicchitta, C. (1999). Receptor mediated and fluid phase pathways for internalization of the ER Hsp90 chaperone GRP94 in murine macrophages. J. Cell Science 112: 2167–2175.
Wells, A., Rai, S., Salvato, M., Band, H., and Malkovsky, M. (1998). Hsp 72-mediated augmentation of MHC class I surface expression and endogeneous antigen presentation. Int. Immunol. 10: 609–617.
Wiest, D., Bhandoola, A., Punt, J., Kreibich, G., McKean, D. and Singer, A. (1997). Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of “ER-resident” molecular chaperones. Proc. Natl. Acad. Sci. USA 91. 1884–1889.
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Robert, J., Ménoret, A., Srivastava, P.K., Cohen, N. (2001). Immunological Properties of Heat Shock Proteins are Phylogenetically Conserved. In: Beck, G., Sugumaran, M., Cooper, E.L. (eds) Phylogenetic Perspectives on the Vertebrate Immune System. Advances in Experimental Medicine and Biology, vol 484. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1291-2_23
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