Key Points
-
Heat-shock proteins (HSPs) are the most abundant group of intracellular molecules and are present in all cells of all organisms.
-
Some HSPs (gp96, HSP90, HSP70, HSP110, GRP170 and calreticulin) are peptide-binding proteins.
-
The HSP-chaperoned peptides are derived from a variety of cellular proteins. The HSP–peptide complexes that are purified from a cell therefore represent the peptide fingerprint of that cell.
-
HSP–peptide complexes that are purified from cancers contain the peptides derived from normal proteins, but also peptides derived from tumour antigens. Similarly, HSP–peptide complexes purified from cells infected with viruses or other pathogens contain pathogen-derived peptides, as well as normal peptides.
-
Immunization of mammals with HSP–peptide complexes elicits potent CD8+ and CD4+ T-cell responses against the HSP-chaperoned peptides. The response is restricted, however, to the foreign or mutated peptides; HSP-associated normal self-peptides do not elicit autoimmune responses.
-
Femtomoles of peptides, if chaperoned by HSPs, are immunogenic. Unchaperoned peptides or peptides that are chaperoned by other proteins do not elicit T-cell responses even at quantities that are higher by several logarithms.
-
The secret of the extraordinary immunogenicity of HSPs lies in a receptor on antigen-presenting cell CD91, which is also the receptor for serum protein α2 macroglobulin.
-
HSP-chaperoned peptides enter the macrophage/dendritic cells through CD91 and are processed and presented by the MHC class I and MHC class II molecules, resulting in the consequent stimulation of CD8+ and CD4+ T cells. At the same time, the HSP–dendritic-cell interaction through CD91 and other receptors leads to maturation of dendritic cells and secretion of an array of pro-inflammatory cytokines.
-
Through their interaction with macrophage and dendritic cells, HSPs are therefore able to stimulate peptide-specific (adaptive), as well as non-specific (innate), components of the immune response.
-
The ability of HSPs to chaperone antigenic peptides and to interact with dendritic cells has led to a new generation of prophylactic and therapeutic candidate vaccines against cancers and infectious diseases.
Abstract
Heat-shock proteins (HSPs) are the most abundant and ubiquitous soluble intracellular proteins. In single-cell organisms, invertebrates and vertebrates, they perform a multitude of housekeeping functions that are essential for cellular survival. In higher vertebrates, their ability to interact with a wide range of proteins and peptides — a property that is shared by major histocompatibility complex molecules — has made the HSPs uniquely suited to an important role in organismal survival by their participation in innate and adaptive immune responses. The immunological properties of HSPs enable them to be used in new immunotherapies of cancers and infections.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ritossa, F. A new puffing pattern induced by temperature shock and DNP in Drosophila. Experientia 18, 571–573 (1962).
Lindquist. S. & Craig, E. A. The heat-shock proteins. Annu. Rev. Genet. 22, 631–677 (1988).
Gething, M. J., Sambrook, J. Protein folding in the cell. Nature 355, 33–45 (1992).
Parsell, D. A. & Lindquist, S. The function of heat-shock proteins in stress tolerance: degradation and reactivation of damaged proteins. Annu. Rev. Genet. 27, 437–496 (1993).
Haas, I. G. BiP — a heat shock protein involved in immunoglobulin chain assembly. Curr. Top. Microbiol. Immunol. 167, 71–82 (1991).
Lindquist, S. The heat-shock response. Annu. Rev. Biochem. 55, 1151–1191 (1986).
Rutherford, S. L. & Lindquist, S. Hsp90 as a capacitor for morphological evolution Nature 396, 336–342 (1998).
Morimoto, R. I. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes. Dev. 12, 3788–3796 (1998).
Feder, M. E. & Hofmann, G. E. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu. Rev. Physiol. 61, 243–282 (1999).
Srivastava, P. K., Menoret, A., Basu, S., Binder, R. J. & McQuade, K. L. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity 8, 657–665 (1998).
Srivastava, P. K. & Das, M. R. Serologically unique surface antigen of a rat hepatoma is also its tumor-associated transplantation antigen. Int. J. Cancer 33, 417–422 (1984).
Srivastava, P. K., DeLeo, A. B. & Old, L. J. Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc. Natl Acad. Sci. USA 83, 3407–3411 (1986).
Ullrich, S. J., Robinson, E. A., Law L. W., Willingham, M. & Appella, E. A mouse tumor-specific transplantation antigen is a heat shock-related protein. Proc. Natl Acad. Sci. 83, 3121–3125 (1986).
Udono, H. & Srivastava, P. K. Heat shock protein 70-associated peptides elicit specific cancer immunity. J. Exp. Med. 178, 1391–1396 (1993).Provides the first formal evidence for the hypothesis (see reference 80 ) that it is the HSP-associated peptides and not the HSPs per se , that are responsible for the immunogenicity of homogeneous HSP70 preparations. It was also the first study that extended the model developed on the basis of gp96 (see references 11–13 ) to another HSP.
Tamura, Y., Peng, P., Kang, L., Daou, M. & Srivastava, P. K. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 278, 117–120 (1997).Shows that HSP–peptide complexes could be used successfully, not only for prophylaxis (as several previous studies had shown), but also for therapy of a wide variety of pre-existing cancers, including a spontaneous melanoma, a spontaneous lung carcinoma, a chemically induced colon carcinoma and a fibrosarcoma. This study has been a primary basis for the large number of the completed and ongoing human clinical trials with tumour-derived HSP–peptide complexes (see references 73,74).
Basu, S. & Srivastava, P. K. Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity. J. Exp. Med. 189, 797–802 (1999).
Wang, X. Y., Kazim, L., Repasky, E. A. and Subjeck, J. R. Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccine activity. J. Immunol. 166, 490–497 (2001).
Ishii, T. et al. Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96. J. Immunol. 162, 1303–1309 (1999).
Ménoret, A. & Srivastava, P. K. Association of peptides with heat shock protein gp96 occurs in vivo and not after cell lysis. Biochem. Biophys. Res. Commun. 262, 813–818 (1999).
Zhu, X. et al. Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272, 1606–1614 (1996).
Linderoth, N. A., Popowicz, A., Sastry, S. Identification of the peptide-binding site in the heat shock chaperone/tumor rejection antigen gp96 (Grp94). J. Biol. Chem. 275, 5472–5477 (2000).
Yamazaki, K., Nguyen, T. & Podack, E. R. Cutting Edge: tumor secreted heat shock-fusion protein elicits CD8 cells for rejection. J Immunol. 163, 5178–5182 (1999).
Zheng, H., Dai, J., Stoilova, D. & Li, Z. Surface targeting of an intracellular heat shock protein gp96 on tumor cells induces dendritic cell maturation and anti–tumor immunity. J. Immunol. 167, 6731–6735 (2001).
Suto, R. & Srivastava, P. K. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269, 1585–1588 (1995).Provides the first mechanistic insight into the immunogenicity of HSP–peptide complexes. It shows that exogenous gp96 is taken up by macrophage in which gp96-associated peptides are processed and routed for presentation by MHC class I molecules through the endogenous pathway.
Arnold, D., Faath, S., Rammensee, H. & Schild, H. Cross-priming of minor histocompatibility antigen-specific cytotoxic T cells upon immunization with the heat shock protein gp96. J. Exp. Med. 182, 885–888 (1995).Independently confirms that immunization with gp96 preparations elicits specific T-cell responses against the antigens expressed by the tissue from which gp96 was isolated. In addition, the authors showed the ability of gp96 preparations to cross–prime, as predicted in references. 36 and also shown in references. 24.
Nieland, T. J. et al. Isolation of an immunodominant viral peptide that is endogenously bound to the stress protein GP96/GRP94. Proc. Natl Acad. Sci. USA 93, 6135–6139 (1996).The first structural demonstration of the association of a known antigenic peptide with gp96, as proposed in reference 80.
Blachere, N. E. et al. Heat shock protein-peptide complexes, reconstituted in vitro, elicit, peptide-specific cytotoxic T lymphocyte response and tumor immunity. J. Exp. Med. 186, 1315–1322 (1997).Shows that HSPs could be charged with antigenic peptides in vitro and that HSP–peptide complexes reconstituted in vitro were immunogenic, like the complexes isolated from cells. This study showed HSPs to be the first adjuvants of mammalian origin.
Yewdell, J. W., Norbury, C. C. & Bennink, J. R. Mechanisms of exogenous antigen presentation by MHC class I molecules in vitro and in vivo: implications for generating CD8+ T cell responses to infectious agents, tumors, transplants, and vaccines. Adv. Immunol. 73, 1–77 (1999).
Matsutake, T. & Srivastava, P. K. CD91 is involved in MHC class II presentation of gp96–chaperoned peptides. Cell Stress Chaperones 5, 378 (2000).
Suzue, K., Zhou, X., Eisen, H. N. & Young, R. A. Heat shock fusion proteins as vehicles for antigen delivery into the major histocompatibility complex class I presentation pathway. Proc. Natl Acad. Sci. USA 94, 13146–13151 (1997).
Cheng, W. F. et al. Enhancement of Sindbis virus self-replicating RNA vaccine potency by linkage of Mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene. J. Immunol. 166, 6218–6226 (2001).
Udono, H., Yamano, T., Kawabata, Y., Ueda, M. & Yui, K. Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70. Int. Immunol. 13, 1233–1242 (2001).
Martin, S. et al. Peptide immunization indicates that CD8+ T cells are the dominant effector cells in trinitrophenyl-specific contact hypersensitivity. J. Invest. Dermatol. 115, 260–266 (2000).
Abiru, N. et al. Peptide and major histocompatibility complex-specific breaking of humoral tolerance to native insulin with the B9-23 peptide in diabetes-prone and normal mice. Diabetes 50, 1274–1281 (2001).
Binder, R. J., Han, D. K. & Srivastava, P. K. CD91 is a receptor for heat shock protein gp96. Nature Immunol. 1, 151–155 (2000).The HSP receptor hypothesized in 1993 (see reference 36 ) was isolated, identified and characterized structurally and functionally.
Srivastava, P. K., Udono, H., Blachere, N. E. & Li, Z. Heat shock proteins transfer peptides during antigen processing and CTL priming. Immunogenetics 39, 93–98 (1994).Anticipated key aspects of the roles of HSPs in the immune response. It suggested the role of HSPs in antigen presentation and in cross-priming, and hypothesized the existence of an HSP receptor on APCs.
Singh-Jasuja, H. et al. Cross-presentation of glycoprotein 96-associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis. J. Exp. Med. 191, 1965–1974 (2000).
Basu, S., Binder, R. J., Ramalingam, T. & Srivastava, P. K. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14, 303–313 (2001).Shows that the CD91 receptor expressed by APCs is the only receptor involved in uptake of HSP–peptide complexes, leading to representation of the chaperoned peptides by MHC class I molecules.
Castellino, F. et al. Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways. J. Exp. Med. 191, 1957–1964 (2000).Provides the first evidence for the re-presentation of HSP70-chaperoned peptides by macrophages through an HSP receptor, and elucidates the intracellular mechanisms involved in such re-presentation.
Castelli, C. et al. Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells. Cancer Res. 61, 222–227 (2001).
Basu, S., Binder, R. J., Suto, R., Anderson, K. M. & Srivastava, P. K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver maturation signal to dendritic cells and activate the NFκB pathway. Int. Immunol. 12, 1539–1546 (2000).Shows the full spectrum of innate immune responses, from translocation of NF-κB into the nucleus to secretion of cytokines to maturation of DCs, set in motion by the interaction of HSPs with macrophages and DCs. It also shows that necrotic but not apoptotic cell death results in release of HSPs, which then cause maturation of DCs.
Panjwani, N. N., Popova, L. & Srivastava, P. K. Heat shock proteins gp96 and hsp70 activate release of nitric oxide by antigen presenting cells. J. Immunol. (in the press).
More, S. H., Breloer, M. & von Bonin, A. Eukaryotic heat shock proteins as molecular links in innate and adaptive immune responses: Hsp60-mediated activation of cytotoxic T cells. Int. Immunol. 13, 1121–1127 (2001).
Lehner, T. et al. Heat shock proteins generate β-chemokines which function as innate adjuvants enhancing adaptive immunity. Eur. J. Immunol. 30, 594–603 (2000).
Singh-Jasuja, H. et al. The heat shock protein gp96 induces maturation of dendritic cells and down-regulation of its receptor. Eur. J. Immunol. 30, 2211–2215 (2000).
Somersan, S. et al. Primary tumor tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells. J. Immunol. 167, 4844–4845 (2001).
Binder, R. J., Anderson, K. M., Basu, S. & Srivastava, P. K. Cutting edge: heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo. J. Immunol. 165, 6029–6035 (2000).
Ohashi, K., Burkart, V., Flohe, S. & Kolb, H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 164, 558–561 (2000).
Vabulas, R. M. et al. Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J. Biol. Chem. 276, 31332–31339 (2001).
Sasu, S., LaVerda, D., Qureshi, N., Goldenbock, D. T. & Beasley, D. Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/p42 mitogen-activated protein kinase activation. Circ. Res. 89, 244–250 (2001).
Habich, C., Baungart, K., Kolb, H. & Burkhart, V. The receptor for hsp60 on macrophages is saturable, specific and distinct from the receptors for other heat shock proteins. J. Immunol. 168, 569–576 (2002).
Lipsker, D. et al. Heat shock proteins 70 and 60 share common receptors which are expressed on human monocyte-derived but not epidermal dendritic cells. Eur. J. Immunol. 32, 322–332 (2002).
Panjwani, N. N., Popova, L., Febbraio, M. & Srivastava, P. K. The CD36 scavenger receptor as a receptor for gp96. Cell Stress Chaperones 5, 391 (2000).
Wang, Y. et al. CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 15, 971–983 (2001).
Hilf, N. et al. The heat shock protein gp96 binds specifically to human platelets. Cell Stress Chaperones 5, 386 (2000).
Botzler, C., Li, G., Issels, R. D. & Multhoff, G. Definition of extracellular localized epitopes of Hsp70 involved in an NK immune response. Cell Stress Chaperones 3, 6–11 (1998).
Verma, R. et al. Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol. Biol. Cell. 11, 3425–3439 (2000).
Cresswell, P., Bangia, N., Dick, T. & Diedrich, G. The nature of the MHC class I peptide loading complex. Immunol. Rev. 172, 21–28 (1999).
Wigley, W. C. et al. Dynamic association of proteasomal machinery with the centrosome. J. Cell Biol. 145, 481–490 (1999).
Anderson, S. L. et al. The endoplasmic reticular heat shock protein gp96 is transcriptionally upregulated in interferon-treated cells. J. Exp. Med. 180, 1565–1569 (1994).
Johnson, A. E. & van Waes, M. A. The translocon: a dynamic gateway at the ER membrane. Annu. Rev. Cell Dev. Biol. 15, 799–842 (1999).
Benkovic, S. J., Valentine, A. M. & Salinas, F. Replisome-mediated DNA replication. Annu. Rev. Biochem. 70, 181–208 (2001).
Wells, A. D., Rai, S. K., Salvato, M. S., Band, H. & Malkovsky, M. Hsp72-mediated augmentation of MHC class I surface expression and endogenous antigen presentation. Int. Immunol. 10, 609–617 (1998).
Chen, D. & Androlewicz, M. J. Heat shock protein 70 moderately enhances peptide binding and transport by the transporter associated with antigen processing. Immunol. Lett. 75, 143–148 (2001).
Binder, R. J., Blachere, N. E. & Srivastava, P. K. Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules. J. Biol. Chem. 276, 17163–17171 (2001).
Arnold, D., Wahl, C., Faath, S., Rammensee, H. G. & Schild, H. Influences of transporter associated with antigen processing (TAP) on the repertoire of peptides associated with the endoplasmic reticulum – resident stress protein gp96. J. Exp. Med. 186, 461–466 (1997).
Menoret, A., Niswonger, M. L., Altmeyer, A. & Srivastava, P. K. An ER protein implicated in chaperoning peptides to MHC class I is an aminopeptidase. J. Biol. Chem. Jun 7 [epub ahead of print] (2001).
Li, Z. & Srivastava, P. K. Tumor rejection antigen Gp96/Grp94 is an ATPase: implications for protein folding and antigen presentation. EMBO J. 12, 3143–3151 (1993).
Serwold, T., Gaw, S. & Shastri, N. ER aminopeptidases generate a unique pool of peptides for MHC class I molecules. Nature Immunol. 2, 644–651 (2001).
Srivastava, P. K. & Old, L. J. Individually distinct transplantation antigens of chemically induced mouse tumors. Immunol. Today 9, 78–83 (1988).
Srivastava, P. K. Do human cancers express shared protective antigens? or the necessity of remembrance of things past. Semin. Immunol. 8, 295–302 (1996).
Janetzki, S., Polla, D., Rosenhauer, V., Lochs, H. & Srivastava, P. K. Immunization of cancer patients with autologous cancer-derived heat shock protein gp96: a pilot study. Int. J. Cancer 88, 232–238 (2000).
Srivastava, P. K., Kumar, S. & Mendonca, C. Principles and practice of the use of heat shock protein-peptide complexes for immunotherapy of human cancer. Principles Practice Biol. Ther. Cancer Updates 2, 1–11 (2001).
Srivastava, P. K. Immunotherapy of human cancer. Lessons from mice. Nature Immunol. 1, 363–366 (2000).
Blachere, N. E. et al. Heat shock protein vaccines against cancer. J. Immunother. 14, 352–356 (1993).
Heikema, A., Agsteribbe, E., Wiscjut, J. & Huckriede, A. Generation of heat shock protein-based vaccines by intracellular loading of gp96 with antigenic peptides. Immunol. Lett. 57, 69–74 (1997).
Ciupitu, A. M. et al. Immunization with a lymphocytic choriomeningitis virus peptide mixed with heat shock protein 70 results in protective antiviral immunity and specific cytotoxic T lymphocytes. J. Exp. Med. 187, 685–691 (1998).
Moroi, Y. et al. Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70. Proc. Natl Acad. Sci. USA 97, 3485–3490 (2000).
Zugel, U., Sponaas, A. M., Neckermann, J., Schoel, B. & Kaufmann, S. H. gp96-peptide vaccination of mice against intracellular bacteria. Infect Immun 69, 4164–4167 (2001).This is the first demonstration of the protective immunogenicity of gp96–peptide complexes isolated from cells infected with intracellular bacteria, against subsequent infection with the bacterium. See references 75–78 and 95 for comparable studies with viral infections.
Srivastava, P. K. & Maki, R. G. Stress-Induced proteins as tumor antigens. Curr.Top. Microbiol. Immunol. 167, 109–124 (1991).
Hill, A. et al. Herpes simplex virus turns off the TAP to evade host immunity. Nature 375, 411–415 (1995).
Randow, F. & Seed, B. Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nature Cell Biol. 3, 891–896 (2001).
Xiao, X. et al. HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice. EMBO J. 18, 5943–5952 (1999).
Rammensee, H., Bachmann, J., Emmerich, N. P., Bachor, O. A. & Stevanovic, S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50, 213–219 (1999).
Blond-Elguindi, S. et al. Affinity panning of a library of peptides displayed on bacteriophages reveals the binding specificity of BiP. Cell 75, 717–728 (1993).
Porgador, A., Yewdell, J. W., Deng, Y., Bennink, J. R. & Germain, R. N. Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody. Immunity 6, 715–726 (1997).
Prodromou, C. et al. Identification and structural characterization of the AYP/ADP-binding site in the hsp90 molecular chaperone. Cell 90, 65–70 (1997).
Melcher, A. et al. Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nature Med. 4, 581–587 (1998).Shows that necrotic, but not apoptotic, cell death is associated with immune responses against dying cells. It further indicated (see reference 89 ) that necrotic death results in upregulation of expression of HSP70 and that increased expression of HSP70 causes increased immunogenicity.
Menoret, A., Patry, Y., Burg, C., Le & Pendu, J. Co-segregation of tumor immunogenicity with expression of inducible but not constitutive hsp70 in rat colon carcinomas. J. Immunol. 155, 740–747 (1995).
Vanaja, D. K., Grossmann, M. E., Celis, E. & Young, C. Y. Tumor prevention and antitumor immunity with heat shock protein 70 induced by 15-deoxy-Δ 12,14-prostaglandin J2 in transgenic adenocarcinoma of mouse prostate cells. Cancer Res. 60, 4714–4718 (2000).
Clark, P. R. & Menoret, A. The inducible Hsp70 as a marker of tumor immunogenicity. Cell Stress Chaparones 6, 121–125 (2001).
Chandawarkar, R. Y., Wagh, M. S. & Srivastava, P. K. The dual nature of specific immunological activity of tumor-derived gp96 preparations. J. Exp. Med. 189, 1437–1442 (1999).
Armstrong, P. B. & Quigley, J. P. α2 macroglobulin: an evolutionary conserved arm of the innate immune system. Dev. Comp. Immunol. 23, 375–390 (1999).
Binder, R. J., Karimeddini, D. & Srivastava, P. K. Adjuvanticity of α2-macroglobulin, an independent ligand for the heat shock protein receptor CD91. J. Immunol. 166, 4968–4972 (2001).
Navaratnam, M., Deshpande, M. S., Hariharan, M. J., Zatechka, D. S. & Srikumaran, S. Heat shock protein-peptide complexes elicit cytotoxic T-lymphocyte and antibody responses specific for bovine herpesvirus 1. Vaccine 19, 1425–1434 (2001).
Meng, S. D., Gao, T., Gao, G. F. & Tien, P. HBV-specific peptide associated with heat-shock protein gp96. Lancet 357, 528–529 (2001).
Breloer, M., Marti, T., Fleischer, B. & von Bonin, A. Isolation of processed, H-2Kb-binding ovalbumin-derived peptides associated with the stress proteins HSP70 and gp96. Eur. J. Immunol. 28, 1016–1021 (1998).
Author information
Authors and Affiliations
Related links
Related links
DATABASES
FURTHER INFORMATION
Pramod Srivastava's lab and others active in the area of the roles of HSPs in immune response
A comprehensive listing of key papers
chaperones, chaperonin and heat-shock proteins
antigen presentation to lymphocytes
Glossary
- PEPTIDE FINGERPRINT
-
Unique collection of all peptides generated in a cell or tissue.
- ANTIGENIC FINGERPRINT
-
Unique collection of all the peptides generated in a cell, tumour or virus-infected tissue that are presented to T-cells.
- CROSS-PRIMING
-
An antigen-expressing cell might not directly stimulate the T cells that recognize that antigen. Instead, the antigen must often be transferred from the antigen-expressing cell to a specialized immune cell (most probably a dendritic cell) that then stimulates the cognate naive T cell. Also known as indirect presentation.
- NUCLEAR FACTOR-κB
-
A transcriptional factor that normally resides in the cytosol, but which on stimulation of the cells with certain ligands, translocates to the nucleus where it initiates the transcription of a wide array of immunologically important genes.
Rights and permissions
About this article
Cite this article
Srivastava, P. Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2, 185–194 (2002). https://doi.org/10.1038/nri749
Issue Date:
DOI: https://doi.org/10.1038/nri749
This article is cited by
-
TRPA1 activation and Hsp90 inhibition synergistically downregulate macrophage activation and inflammatory responses in vitro
BMC Immunology (2023)
-
Activation of immune signals during organ transplantation
Signal Transduction and Targeted Therapy (2023)
-
Introducing Molecular Chaperones into the Causality and Prospective Management of Autoimmune Hepatitis
Digestive Diseases and Sciences (2023)
-
Acute toxic effects of microcystin-LR on crayfish (Procambarus clarkii): Insights from antioxidant system, histopathology and intestinal flora
Environmental Science and Pollution Research (2023)
-
Impact of different levels of handling on Solea senegalensis culture: effects on growth and molecular markers of stress
Fish Physiology and Biochemistry (2023)