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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2011

Open Access 01-12-2011 | Research

Heat shock protein 70/peptide complexes: potent mediators for the generation of antiviral T cells particularly with regard to low precursor frequencies

Authors: Sabine Tischer, Megan Basila, Britta Maecker-Kolhoff, Stephan Immenschuh, Mathias Oelke, Rainer Blasczyk, Britta Eiz-Vesper

Published in: Journal of Translational Medicine | Issue 1/2011

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Abstract

Background

Heat shock protein 70 (HSP70) has gained major attention as an adjuvant capable of inducing antigen-specific CD8+ and CD4+ T-cell responses. The ability of HSP70/peptide complexes to elicit cytotoxic T-cell (CTL) responses by cross-presentation of exogenous antigens via HLA class I molecules is of central interest in immunotherapy. We examined the role of HSP70/CMVpp65495-503-peptide complex (HSP70/CMV-PC) in HLA class I-restricted cross-presentation for ex vivo expansion of CMV-specific CTLs.

Methods

CMV-specific T cells generated from PBMCs of HLA-A*02:01/CMV-seropositive donors were stimulated for 21 days with HSP70/CMV-PC and analyzed in functional assays. As a control PBMCs were cultured in the presence of CMVpp65495-503 peptide or HSP70. Increase of CMV-specific CTLs was visualized by pentameric HLA-A*02:01/CMVpp65495-503 complex.

Results

About 90% of HSP70/CMV-PC generated T cells were CMV-specific and exhibited significantly higher IFN-γ secretion, cytotoxic activity, and an increased heme oxygenase 1 (HO-1) gene expression as compared to about 69% of those stimulated with CMVpp65495-503 peptide. We decided to classify the HLA-A*02:01/CMV-seropositive donors as weak, medium, and strong responder according to the frequency of generated A2/CMV-pentamer-positive CD8+ T cells. HSP70/CMV-PC significantly induces strong antiviral T-cell responses especially in those donors with low memory precursor frequencies. Blockage of CD91 with α2-macroglobulin markedly reduced proliferation of antiviral T cells suggesting a major role of this receptor in the uptake of HSP70/CMV-PC.

Conclusion

This study clearly demonstrates that HSP70/CMV-PC is a potent mediator to induce stronger T-cell responses compared to antiviral peptides. This simple and efficient technique may help to generate significant quantities of antiviral CTLs by cross-presentation. Thus, we propose HSP70 for chaperoning peptides to reach an efficient level of cross-presentation. HSP70/peptide complexes may be particularly useful to generate stronger T-cell responses in cases of low precursor frequencies and may help to improve the efficiency of antigen-specific T-cell therapy for minor antigens.
Appendix
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Literature
1.
Calderwood SK, Gong J, Theriault JR, Mambula SS, Gray PJ: Cell stress proteins: novel immunotherapeutics. Novartis Found Symp. 2008, 291: 115-131. discussion 131-140CrossRefPubMed
2.
Beere HM: Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Invest. 2005, 115: 2633-2639. 10.1172/JCI26471.PubMedCentralCrossRefPubMed
3.
Chen T, Guo J, Han C, Yang M, Cao X: Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via TLR4 pathway. J Immunol. 2009, 182: 1449-1459.CrossRefPubMed
4.
Hoos A, Levey DL: Vaccination with heat shock protein-peptide complexes: from basic science to clinical applications. Expert Rev Vaccines. 2003, 2: 369-379. 10.1586/14760584.2.3.369.CrossRefPubMed
5.
Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A: Phase III comparison of vitespen, an autologous tumor-derived heat shock protein gp96 peptide complex vaccine, with physician's choice of treatment for stage IV melanoma: the C-100-21 Study Group. J Clin Oncol. 2008, 26: 955-962. 10.1200/JCO.2007.11.9941.CrossRefPubMed
6.
Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F: An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet. 2008, 372: 145-154. 10.1016/S0140-6736(08)60697-2.CrossRefPubMed
7.
Srivastava PK, Callahan MK, Mauri MM: Treating human cancers with heat shock protein-peptide complexes: the road ahead. Expert Opin Biol Ther. 2009, 9: 179-186. 10.1517/14712590802633918.CrossRefPubMed
8.
Binder RJ, Srivastava PK: Peptides chaperoned by heat-shock proteins are a necessary and sufficient source of antigen in the cross-priming of CD8+ T cells. Nat Immunol. 2005, 6: 593-599.CrossRefPubMed
9.
Flechtner JB, Cohane KP, Mehta S, Slusarewicz P, Leonard AK, Barber BH, Levey DL, Andjelic S: High-affinity interactions between peptides and heat shock protein 70 augment CD8+ T lymphocyte immune responses. J Immunol. 2006, 177: 1017-1027.CrossRefPubMed
10.
Valentinis B, Capobianco A, Esposito F, Bianchi A, Rovere-Querini P, Manfredi AA, Traversari C: Human recombinant heat shock protein 70 affects the maturation pathways of dendritic cells in vitro and has an in vivo adjuvant activity. J Leukoc Biol. 2008, 84: 199-206. 10.1189/jlb.0807548.CrossRefPubMed
11.
Somersan S, Larsson M, Fonteneau JF, Basu S, Srivastava P, Bhardwaj N: Primary tumor tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells. J Immunol. 2001, 167: 4844-4852.CrossRefPubMed
12.
Bajor A, Tischer S, Figueiredo C, Wittmann M, Immenschuh S, Blasczyk R, Eiz-Vesper B: Modulatory role of calreticulin as chaperokine for dendritic cell-based immunotherapy. Clin Exp Immunol. 165: 220-234.
13.
Binder RJ: Hsp receptors: the cases of identity and mistaken identity. Curr Opin Mol Ther. 2009, 11: 62-71.PubMed
14.
Basu S, Binder RJ, Ramalingam T, Srivastava PK: CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity. 2001, 14: 303-313. 10.1016/S1074-7613(01)00111-X.CrossRefPubMed
15.
Binder RJ, Han DK, Srivastava PK: CD91: a receptor for heat shock protein gp96. Nat Immunol. 2000, 1: 151-155. 10.1038/77835.CrossRefPubMed
16.
Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK: Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem. 2002, 277: 15028-15034. 10.1074/jbc.M200497200.CrossRefPubMed
17.
Vabulas RM, Wagner H, Schild H: Heat shock proteins as ligands of toll-like receptors. Curr Top Microbiol Immunol. 2002, 270: 169-184. 10.1007/978-3-642-59430-4_11.PubMed
18.
Delneste Y, Magistrelli G, Gauchat J, Haeuw J, Aubry J, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J, Jeannin P: Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity. 2002, 17: 353-362. 10.1016/S1074-7613(02)00388-6.CrossRefPubMed
19.
Becker T, Hartl FU, Wieland F: CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol. 2002, 158: 1277-1285. 10.1083/jcb.200208083.PubMedCentralCrossRefPubMed
20.
SenGupta D, Norris PJ, Suscovich TJ, Hassan-Zahraee M, Moffett HF, Trocha A, Draenert R, Goulder PJ, Binder RJ, Levey DL: Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II. J Immunol. 2004, 173: 1987-1993.CrossRefPubMed
21.
Einsele H, Kapp M, Grigoleit GU: CMV-specific T cell therapy. Blood Cells Mol Dis. 2008, 40: 71-75. 10.1016/j.bcmd.2007.07.002.CrossRefPubMed
22.
Comoli P, Basso S, Labirio M, Baldanti F, Maccario R, Locatelli F: T cell therapy of Epstein-Barr virus and adenovirus infections after hemopoietic stem cell transplant. Blood Cells Mol Dis. 2008, 40: 68-70. 10.1016/j.bcmd.2007.06.020.CrossRefPubMed
23.
Moosmann A, Bigalke I, Tischer J, Schirrmann L, Kasten J, Tippmer S, Leeping M, Prevalsek D, Jaeger G, Ledderose G: Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood.
24.
Feuchtinger T, Richard C, Joachim S, Scheible MH, Schumm M, Hamprecht K, Martin D, Jahn G, Handgretinger R, Lang P: Clinical grade generation of hexon-specific T cells for adoptive T-cell transfer as a treatment of adenovirus infection after allogeneic stem cell transplantation. J Immunother. 2008, 31: 199-206. 10.1097/CJI.0b013e31815ef862.CrossRefPubMed
25.
Brestrich G, Zwinger S, Roemhild A, Noutsias M, Rohde M, Keeren K, Sawitzki B, Volk HD, Reinke P, Hammer MH: Generation of HCMV-specific T-cell lines from seropositive solid-organ-transplant recipients for adoptive T-cell therapy. J Immunother. 2009, 32: 932-940. 10.1097/CJI.0b013e3181b88fda.CrossRefPubMed
26.
Savoldo B, Goss JA, Hammer MM, Zhang L, Lopez T, Gee AP, Lin YF, Quiros-Tejeira RE, Reinke P, Schubert S: Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs). Blood. 2006, 108: 2942-2949. 10.1182/blood-2006-05-021782.PubMedCentralCrossRefPubMed
27.
Hoffman JA: Adenovirus infections in solid organ transplant recipients. Curr Opin Organ Transplant. 2009, 14: 625-633. 10.1097/MOT.0b013e3283324e1b.CrossRefPubMed
28.
Leen AM, Christin A, Myers GD, Liu H, Cruz CR, Hanley PJ, Kennedy-Nasser AA, Leung KS, Gee AP, Krance RA: Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood. 2009, 114: 4283-4292. 10.1182/blood-2009-07-232454.PubMedCentralCrossRefPubMed
29.
Solache A, Morgan CL, Dodi AI, Morte C, Scott I, Baboonian C, Zal B, Goldman J, Grundy JE, Madrigal JA: Identification of three HLA-A*0201-restricted cytotoxic T cell epitopes in the cytomegalovirus protein pp65 that are conserved between eight strains of the virus. J Immunol. 1999, 163: 5512-5518.PubMed
30.
Lilleri D, Fornara C, Chiesa A, Caldera D, Alessandrino EP, Gerna G: Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection. Haematologica. 2008, 93: 248-256. 10.3324/haematol.11912.CrossRefPubMed
31.
Oelke M, Maus MV, Didiano D, June CH, Mackensen A, Schneck JP: Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells. Nat Med. 2003, 9: 619-624. 10.1038/nm869.CrossRefPubMed
32.
Paine A, Oelke M, Blasczyk R, Eiz-Vesper B: Expansion of human cytomegalovirus-specific T lymphocytes from unfractionated peripheral blood mononuclear cells with artificial antigen-presenting cells. Transfusion. 2007, 47: 2143-2152. 10.1111/j.1537-2995.2007.01439.x.CrossRefPubMed
33.
Peggs KS, Verfuerth S, Pizzey A, Chow SL, Thomson K, Mackinnon S: Cytomegalovirus-specific T cell immunotherapy promotes restoration of durable functional antiviral immunity following allogeneic stem cell transplantation. Clin Infect Dis. 2009, 49: 1851-1860. 10.1086/648422.CrossRefPubMed
34.
Rauser G, Einsele H, Sinzger C, Wernet D, Kuntz G, Assenmacher M, Campbell JD, Topp MS: Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants. Blood. 2004, 103: 3565-3572. 10.1182/blood-2003-09-3056.CrossRefPubMed
35.
Figueiredo C, Wittmann M, Wang D, Dressel R, Seltsam A, Blasczyk R, Eiz-Vesper B: Heat shock protein 70 (HSP70) induces cytotoxicity of T-helper cells. Blood. 2009, 113: 3008-3016. 10.1182/blood-2008-06-162727.CrossRefPubMed
36.
Blachere NE, Li Z, Chandawarkar RY, Suto R, Jaikaria NS, Basu S, Udono H, Srivastava PK: Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J Exp Med. 1997, 186: 1315-1322. 10.1084/jem.186.8.1315.PubMedCentralCrossRefPubMed
37.
Li Z: In vitro reconstitution of heat shock protein-peptide complexes for generating peptide-specific vaccines against cancers and infectious diseases. Methods. 2004, 32: 25-28. 10.1016/S1046-2023(03)00183-X.CrossRefPubMed
38.
Paine A, Oelke M, Tischer S, Heuft HG, Blasczyk R, Eiz-Vesper B: Soluble recombinant CMVpp65 spanning multiple HLA alleles for reconstitution of antiviral CD4+ and CD8+ T-cell responses after allogeneic stem cell transplantation. J Immunother. 33: 60-72.
39.
Watanabe K, Suzuki S, Kamei M, Toji S, Kawase T, Takahashi T, Kuzushima K, Akatsuka Y: CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy. Int J Hematol. 2008, 88: 311-320. 10.1007/s12185-008-0134-z.CrossRefPubMed
40.
Vaz-Santiago J, Lule J, Rohrlich P, Jacquier C, Gibert N, Le Roy E, Betbeder D, Davignon JL, Davrinche C: Ex vivo stimulation and expansion of both CD4(+) and CD8(+) T cells from peripheral blood mononuclear cells of human cytomegalovirus-seropositive blood donors by using a soluble recombinant chimeric protein, IE1-pp65. J Virol. 2001, 75: 7840-7847. 10.1128/JVI.75.17.7840-7847.2001.PubMedCentralCrossRefPubMed
41.
Wills MR, Carmichael AJ, Mynard K, Jin X, Weekes MP, Plachter B, Sissons JG: The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J Virol. 1996, 70: 7569-7579.PubMedCentralPubMed
42.
Zaia JA, Gallez-Hawkins G, Li X, Yao ZQ, Lomeli N, Molinder K, La Rosa C, Diamond DJ: Infrequent occurrence of natural mutations in the pp65(495-503) epitope sequence presented by the HLA A*0201 allele among human cytomegalovirus isolates. J Virol. 2001, 75: 2472-2474. 10.1128/JVI.75.5.2472-2474.2001.PubMedCentralCrossRefPubMed
43.
Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, Gallino G, Piris A, Cattelan A, Lazzari I: Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol. 2002, 20: 4169-4180. 10.1200/JCO.2002.09.134.CrossRefPubMed
44.
Castelli C, Ciupitu AM, Rini F, Rivoltini L, Mazzocchi A, Kiessling R, Parmiani G: Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells. Cancer Res. 2001, 61: 222-227.PubMed
45.
Rivoltini L, Castelli C, Carrabba M, Mazzaferro V, Pilla L, Huber V, Coppa J, Gallino G, Scheibenbogen C, Squarcina P: Human tumor-derived heat shock protein 96 mediates in vitro activation and in vivo expansion of melanoma- and colon carcinoma-specific T cells. J Immunol. 2003, 171: 3467-3474.CrossRefPubMed
46.
Castellino F, Boucher PE, Eichelberg K, Mayhew M, Rothman JE, Houghton AN, Germain RN: 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. 2000, 191: 1957-1964.PubMedCentralCrossRefPubMed
47.
Noessner E, Gastpar R, Milani V, Brandl A, Hutzler PJ, Kuppner MC, Roos M, Kremmer E, Asea A, Calderwood SK, Issels RD: Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol. 2002, 169: 5424-5432.CrossRefPubMed
48.
Binder RJ, Srivastava PK: Essential role of CD91 in re-presentation of gp96-chaperoned peptides. Proc Natl Acad Sci USA. 2004, 101: 6128-6133. 10.1073/pnas.0308180101.PubMedCentralCrossRefPubMed
49.
Matsutake T, Sawamura T, Srivastava PK: High efficiency CD91- and LOX-1-mediated re-presentation of gp96-chaperoned peptides by MHC II molecules. Cancer Immun. 10: 7-
50.
Kern F, Bunde T, Faulhaber N, Kiecker F, Khatamzas E, Rudawski IM, Pruss A, Gratama JW, Volkmer-Engert R, Ewert R: Cytomegalovirus (CMV) phosphoprotein 65 makes a large contribution to shaping the T cell repertoire in CMV-exposed individuals. J Infect Dis. 2002, 185: 1709-1716. 10.1086/340637.CrossRefPubMed
51.
Bao L, Dunham K, Stamer M, Mulieri KM, Lucas KG: Expansion of cytomegalovirus pp65 and IE-1 specific cytotoxic T lymphocytes for cytomegalovirus-specific immunotherapy following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008, 14: 1156-1162. 10.1016/j.bbmt.2008.07.014.PubMedCentralCrossRefPubMed
52.
Lacey SF, Villacres MC, La Rosa C, Wang Z, Longmate J, Martinez J, Brewer JC, Mekhoubad S, Maas R, Leedom JM: Relative dominance of HLA-B*07 restricted CD8+ T-lymphocyte immune responses to human cytomegalovirus pp65 in persons sharing HLA-A*02 and HLA-B*07 alleles. Hum Immunol. 2003, 64: 440-452. 10.1016/S0198-8859(03)00028-4.CrossRefPubMed
53.
Navaratnam M, Deshpande MS, Hariharan MJ, Zatechka DS, Srikumaran S: Heat shock protein-peptide complexes elicit cytotoxic T-lymphocyte and antibody responses specific for bovine herpesvirus 1. Vaccine. 2001, 19: 1425-1434. 10.1016/S0264-410X(00)00381-9.CrossRefPubMed
54.
Han Y, Guo Q, Zhang M, Chen Z, Cao X: CD69+ CD4+ CD25- T cells, a new subset of regulatory T cells, suppress T cell proliferation through membrane-bound TGF-beta 1. J Immunol. 2009, 182: 111-120.CrossRefPubMed
55.
Wolfl M, Kuball J, Ho WY, Nguyen H, Manley TJ, Bleakley M, Greenberg PD: Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities. Blood. 2007, 110: 201-210. 10.1182/blood-2006-11-056168.PubMedCentralCrossRefPubMed
56.
Clerget M, Polla BS: Erythrophagocytosis induces heat shock protein synthesis by human monocytes-macrophages. Proc Natl Acad Sci USA. 1990, 87: 1081-1085. 10.1073/pnas.87.3.1081.PubMedCentralCrossRefPubMed
57.
Tacchini L, Schiaffonati L, Pappalardo C, Gatti S, Bernelli-Zazzera A: Expression of HSP 70, immediate-early response and heme oxygenase genes in ischemic-reperfused rat liver. Lab Invest. 1993, 68: 465-471.PubMed
58.
Biburger M, Theiner G, Schadle M, Schuler G, Tiegs G: Pivotal Advance: Heme oxygenase 1 expression by human CD4+ T cells is not sufficient for their development of immunoregulatory capacity. J Leukoc Biol. 87: 193-202.
59.
Andersen MH, Sorensen RB, Brimnes MK, Svane IM, Becker JC, thor Straten P: Identification of heme oxygenase-1-specific regulatory CD8+ T cells in cancer patients. J Clin Invest. 2009, 119: 2245-2256. 10.1172/JCI38739.PubMedCentralCrossRefPubMed
60.
Maeda H, Sahara H, Mori Y, Torigo T, Kamiguchi K, Tamura Y, Tamura Y, Hirata K, Sato N: Biological heterogeneity of the peptide-binding motif of the 70-kDa heat shock protein by surface plasmon resonance analysis. J Biol Chem. 2007, 282: 26956-26962. 10.1074/jbc.M703436200.CrossRefPubMed
61.
York IA, Goldberg AL, Mo XY, Rock KL: Proteolysis and class I major histocompatibility complex antigen presentation. Immunol Rev. 1999, 172: 49-66. 10.1111/j.1600-065X.1999.tb01355.x.CrossRefPubMed
62.
Lund BT, Chakryan Y, Ashikian N, Mnatsakanyan L, Bevan CJ, Aguilera R, Gallaher T, Jakowec MW: Association of MBP peptides with Hsp70 in normal appearing human white matter. J Neurol Sci. 2006, 249: 122-134. 10.1016/j.jns.2006.05.066.CrossRefPubMed
Metadata
Title
Heat shock protein 70/peptide complexes: potent mediators for the generation of antiviral T cells particularly with regard to low precursor frequencies
Authors
Sabine Tischer
Megan Basila
Britta Maecker-Kolhoff
Stephan Immenschuh
Mathias Oelke
Rainer Blasczyk
Britta Eiz-Vesper
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2011
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-9-175

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