Hsp receptors: The cases of identity and mistaken identity

Current Opinion in Molecular Therapeutics

Volumn 11, Issue 1, 2009, Pages 62-71

  Binder, R J ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Antigen presenting cell; Chaperone; Scavenger receptor; Tumor immunity

Indexed keywords

CANCER VACCINE; CD14 ANTIGEN; CD40 ANTIGEN; CELL SURFACE RECEPTOR; DACARBAZINE; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN VACCINE; INTERLEUKIN 2; LIGAND; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; OXIDIZED LOW DENSITY LIPOPROTEIN RECEPTOR 1; RECOMBINANT PROTEIN; SCAVENGER RECEPTOR A; TEMOZOLOMIDE; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG; VITESPEN;

ANTIGEN PRESENTING CELL; CLINICAL TRIAL; ENDOTHELIUM CELL; EXPERIMENTAL STUDY; HUMAN; IDENTITY; IMMUNE RESPONSE; IN VIVO STUDY; KIDNEY CARCINOMA; MEDICAL LITERATURE; MELANOMA; MOLECULE; NONHUMAN; PROTEIN INTERACTION; REVIEW;

ANTIGEN-PRESENTING CELLS; HEAT-SHOCK PROTEINS; HUMANS; NEOPLASMS;

EID: 58849156936     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (86)

1. Srivastava PK, Das MR: The serologically unique cell surface antigen of Zajdela ascitic hepatoma is also its tumor-associated transplantation antigen. Int J Cancer (1984) 33(3):417-422.
2. Srivastava PK, DeLeo AB, Old LJ: Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc Natl Acad Sci USA (1986) 83(10):3407-3411.
3. Srivastava P: Interaction of heat shock proteins with peptides and antigen presenting cells: Chaperoning of the innate and adaptive immune responses. Annu Rev Immunol (2002) 20:395-425.
4. Udono H, Levey DL, Srivastava PK: 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 (1994) 91(8):3077-3081.
5. Tamura Y, Peng P, Liu K, Daou M, Srivastava PK: Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science (1997) 278(5335):117-120.
6. Srivastava PK, Udono H, Blachere NE, Li Z: Heat shock proteins transfer peptides during antigen processing and CTL priming. Immunogenetics (1994) 39(2):93-98. •• The existence of Hsp receptors were first proposed in this paper based on the observation that small amounts of Hsps elicited immune responses. Other characteristics to consider when identifying Hsp receptors were also discussed.
7. Suto R, Srivastava PK: A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science (1995) 269(5230):1585-1588.
8. SenGupta D, Norris PJ, Suscovich TJ, Hassan-Zahraee M, Moffett HF, Trocha A, Draenert R, Goulder PJ, Binder RJ, Levey DL, Walker BD et al: Heat shock protein-mediated cross-presentation of exogenous HIV antigen on HLA class I and class II. J Immunol (2004) 173(3):1987-1993.
9. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK: Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway. Int Immunol (2000) 12(11):1539-1546.
10. Chen W, Syldath U, Bellmann K, Burkart V, Kolb H: Human 60-kDa heat-shock protein: A danger signal to the innate immune system. J Immunol (1999) 162(6):3212-3219.
11. Binder RJ, Harris ML, Menoret A, Srivastava PK; Saturation, competition, and specificity in interaction of heat shock proteins (Hsp) gp96, Hsp90, and Hsp70 with CD11b+ cells. J Immunol (2000) 165(5):2582-2587.
12. Arnold-Schild D, Hanau D, Spehner D, Schmid C, Rammensee HG, de la Salle H, Schild H: Cutting edge: Receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells. J Immunol (1999) 162(7):3757-3760.
13. Binder RJ, Vatner R, Srivastava P: The heat-shock protein receptors: Some answers and more questions. Tissue Antigens (2004) 64(4):442-451.
14. Jacobs S, Shechter Y, Bissell K, Cuatrecasas P: Purification and properties of insulin receptors from rat liver membranes. Biochem Biophys Res Commun (1977) 77(3):981-988.
15. 2-adrenergic receptor: Purification and characterization. Biochemistry (1984) 23(20):4510-4518.
16. Binder RJ, Han DK, Srivastava PK: CD91: A receptor for heat shock protein gp96. Nat Immunol (2000) 1(2):151-155. •• CD91 was identified as the first Hsp receptor. CD91 remains the only Hsp receptor for which a physical association between the receptor and its ligand (the Hsp) has been observed.
17. Habich C, Baumgart K, Kolb H, Burkart V: The receptor for heat shock protein 60 on macrophages is saturable, specific, and distinct from receptors for other heat shock proteins. J Immunol (2002) 168(2):569- 576.
18. Banerjee PP, Vinay DS, Mathew A, Raje M, Parekh V, Prasad DV, Kumar A, Mitra D, Mishra GC: Evidence that glycoprotein 96 (B2), a stress protein, functions as a Th2-specific costimulatory molecule. J Immunol (2002) 169(7):3507-3518.
19. Stebbing J, Gazzard B, Portsmouth S, Gotch F, Kim L, Bower M, Mandalia S, Binder R, Srivastava P, Patterson S: Disease-associated dendritic cells respond to disease-specific antigens through the common heat shock protein receptor. Blood (2003) 102(5):1806-1814.
20. Robert J, Ramanayake T, Maniero GD, Morales H, Chida AS: Phylogenetic conservation of glycoprotein 96 ability to interact with CD91 and facilitate antigen cross-presentation. J Immunol (2008) 180(5):3176-3182.
21. Berwin B, Hart JP, Pizzo SV, Nicchitta CV: Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides. J Immunol (2002) 168(9):4282-4286.
22. Binder RJ, Srivastava PK: Essential role of CD91 in re-presentation of gp96-chaperoned peptides. Proc Natl Acad Sci USA (2004) 101(16):6128-6133.
23. 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(3):303-313. • Four immunogenic Hsps utilize CD91 as a receptor on macrophages and DCs.
24. Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, Fadok VA, Henson PM: C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med (2001) 194(6):781-795.
25. Vandivier RW, Ogden CA, Fadok VA, Hoffmann PR, Brown KK, Botto M, Walport MJ, Fisher JH, Henson PM, Greene KE: Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: Calreticulin and CD91 as a common collectin receptor complex. J Immunol (2002) 169(7):3978-3986.
26. Ling S, Pi X, Holoshitz J: The rheumatoid arthritis shared epitope triggers innate immune signaling via cell surface calreticulin. J Immunol (2007) 179(9):6359-6367.
27. Li SS, Liu Z, Uzunel M, Sundqvist KG: Endogenous thrombospondin-1 is a cell-surface ligand for regulation of integrin-dependent T-lymphocyte adhesion. Blood (2006) 108(9):3112-3120.
28. Orr AW, Elzie CA, Kucik DF, Murphy-Ullrich JE: Thrombospondin signaling through the calreticulin/LDL receptor-related protein co-complex stimulates random and directed cell migration. J Cell Sci (2003) 116(14):2917-2927.
29. Orr AW, Pedraza CE, Pallero MA, Elzie CA, Goicoechea S, Strickland DK, Murphy-Ullrich JE: Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly. J Cell Biol (2003) 161(6): 1179-1189.
30. Walters JJ, Berwin B: Differential CD91 dependence for calreticulin and Pseudomonas exotoxin-A endocytosis. Traffic (2005) 6(12):1173-1182.
31. 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(3):353-362. • This study described LOX-1 as a receptor for Hsp70 and refuted the observation that CD14 functioned as a receptor for Hsp70.
32. Martin CA, Carsons SE, Kowalewski R, Bernstein D, Valentino M, Santiago-Schwarz F: Aberrant extracellular and dendritic cell (DC) surface expression of heat shock protein (Hsp)70 in the rheumatoid joint: Possible mechanisms of Hsp/DC-mediated cross-priming. J Immunol (2003) 171(11):5736-5742.
33. Wan T, Zhou X, Chen G, An H, Chen T, Zhang W, Liu S, Jiang Y, Yang F, Wu Y, Cao X: Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant. Blood (2004) 103(5):1747-1754.
34. Tobian AA, Canaday DH, Boom WH, Harding CV: Bacterial heat shock proteins promote CD91-dependent class I MHC cross-presentation of chaperoned peptide to CD8+ T cells by cytosolic mechanisms in dendritic cells versus vacuolar mechanisms in macrophages. J Immunol (2004) 172(9):5277-5286.
35. Tobian AA, Harding CV, Canaday DH: Mycobacterium tuberculosis heat shock fusion protein enhances class I MHC cross-processing and -presentation by B lymphocytes. J Immunol (2005) 174(9):5209- 5214.
36. Cheng CF, Fan J, Fedesco M, Guan S, Li Y, Bandyopadhyay B, Bright AM, Yerushalmi D, Liang M, Chen M, Han YP et al: Transforming growth factor α (TGFα)-stimulated secretion of Hsp90α: Using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFβ-rich environment during wound healing. Mol Cell Biol (2008) 28(10):3344-3358.
37. Barnes H, Larsen B, Tyers M, van der Geer P: Tyrosine-phosphorylated low density lipoprotein receptor-related protein 1 (Lrp1) associates with the adaptor protein SHC in SRC-transformed cells. J Biol Chem (2001) 276(22):19119-19125.
38. Martin AM, Kuhlmann C, Trossbach S, Jaeger S, Waldron E, Roebroek A, Luhmann HJ, Laatsch A, Weggen S, Lessmann V, Pietrzik CU: The functional role of the second NPXY motif of the LRP1 β-chain in tissue-type plasminogen activator-mediated activation of N-methyl-d-aspartate receptors. J Biol Chem (2008) 283(18):12004-12013.
39. Betts GN, van der Geer P, Komives EA: Structural and functional consequences of tyrosine phosphorylation in the LRP1 cytoplasmic domain. J Biol Chem (2008) 283(23):15656-15664.
40. Herz, J, Strickland DK: LRP: A multifunctional scavenger and signaling receptor. J Clin Invest (2001) 108(6):779-784.
41. Stebbing J, Gazzard B, Kim L, Portsmouth S, Wildfire A, Teo I, Nelson M, Bower M, Gotch F, Shaunak S, Srivastava P, Patterson S: The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected "true" long-term nonprogressors. Blood (2003) 101(10):4000-4004.
42. Hromadnikova I, Nguyen TT, Zlacka D, Sedlackova L, Popelka S, Veigl D, Pech J, Vavrincova P, Sosna A: Expression of heat shock protein receptors on fibroblast-like synovial cells derived from rheumatoid arthritis-affected joints. Rheumatol Int (2008) 28(9):837-844.
43. Boyman O, Conrad C, Dudli C, Kielhorn E, Nickoloff BJ, Nestle FO: Activation of dendritic antigen-presenting cells expressing common heat shock protein receptor CD91 during induction of psoriasis. Br J Dermatol (2005) 152(6):1211-1218.
44. 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(17):15028-15034.
45. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H: Hsp70 as endogenous stimulus of the toll/interleukin-1 receptor signal pathway. J Biol Chem (2002) 277(17):15107-15112.
46. Dybdahl B, Wahba A, Lien E, Flo TH, Waage A, Qureshi N, Sellevold OF, Espevik T, Sundan A: Inflammatory response after open heart surgery: Release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation (2002) 105(6):685-690.
47. Enomoto Y, Bharti A, Khaleque AA, Song B, Liu C, Apostolopoulos V, Xing PX, Calderwood SK, Gong J: Enhanced immunogenicity of heat shock protein 70 peptide complexes from dendritic cell-tumor fusion cells. J Immunol (2006) 177(9):5946-5955.
48. Galloway E, Shin T, Huber N, Eismann T, Kuboki S, Schuster R, Blanchard J, Wong HR, Lentsch AB: Activation of hepatocytes by extracellular heat shock protein-72. Am J Physiol Cell Physiol (2008) 295(2):C514- C520.
49. Luo X, Zuo X, Zhang B, Song L, Wei X, Zhou Y, Xiao X: Release of heat shock protein 70 and the effects of extracellular heat shock protein 70 on the production of IL-10 in fibroblast-like synoviocytes. Cell Stress Chaperones (2008) 13(3):365-373.
50. Vabulas RM, Braedel S, Hilf N, Singh-Jasuja H, Herter S, Ahmad-Nejad P, Kirschning CJ, Da Costa C, Rammensee HG, Wagner H, Schild H: The endoplasmic reticulum-resident heat shock protein gp96 activates dendritic cells via the toll-like receptor 2/4 pathway. J Biol Chem (2002) 277(23):20847-20853.
51. Liu B, Dai J, Zheng H, Stoilova D, Sun S, Li Z: Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases. Proc Natl Acad Sci USA (2003) 100(26):15824-15829. • Although an Hsp receptor was not identified, gp96-receptor interactions were examined in an LPS-free cell-based system.
52. Warger T, Hilf N, Rechtsteiner G, Haselmayer P, Carrick DM, Jonuleit H, von Landenberg P, Rammensee HG, Nicchitta CV, Radsak MP, Schild H: Interaction of TLR2 and TLR4 ligands with the N-terminal domain of gp96 amplifies innate and adaptive immune responses. J Biol Chem (2006) 281(32):22545-22553.
53. Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Hacker H, Wagner H: 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 (2001) 276(33):31332-31339.
54. 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 (2000) 164(2):558-561.
55. Osterloh A, Veit A, Gessner A, Fleischer B, Breloer M: Hsp60-mediated T cell stimulation is independent of TLR4 and IL-12. Int Immunol (2008) 20(3):433-443. • The issue of contaminating LPS was highlighted in this study. TLR4 no longer functioned as an Hsp receptor when LPS was removed from Hsp preparations.
56. Roelofs MF, Boelens WC, Joosten LA, Abdollahi-Roodsaz S, Geurts J, Wunderink LU, Schreurs BW, van den Berg WB, Radstake TR: Identification of small heat shock protein B8 (Hsp22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J Immunol (2006) 176(11):7021-7027.
57. Gao B, Tsan MF: Endotoxin contamination in recombinant human heat shock protein 70 (Hsp70) preparation is responsible for the induction of tumor necrosis factor α release by murine macrophages. J Biol Chem (2003) 278(1):174-179.
58. Gao B, Tsan MF: Recombinant human heat shock protein 60 does not induce the release of tumor necrosis factor α from murine macrophages. J Biol Chem (2003) 278(25):22523-22529.
59. Bausinger H, Lipsker D, Ziylan U, Manie S, Briand JP, Cazenave JP, Muller S, Haeuw JF, Ravanat C, de la Salle H, Hanau D: Endotoxin-free heat-shock protein 70 fails to induce APC activation. Eur J Immunol (2002) 32(12):3708-3713.
60. Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK: Hsp70 stimulates cytokine production through a CD14-dependent pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med (2000) 6(4):435-442.
61. Asea A, Kabingu E, Stevenson MA, Calderwood SK: Hsp70 peptide-bearing and peptide-negative preparations act as chaperokines. Cell Stress Chaperones (2000) 5(5):425-431.
62. Kol A, Lichtman AH, Finberg RW, Libby P, Kurt-Jones EA: Cutting edge: Heat shock protein (Hsp) 60 activates the innate immune response: CD14 is an essential receptor for Hsp60 activation of mononuclear cells. J Immunol (2000) 164(1):13-17
63. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC: CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science (1990) 249(4975):1431-1433.
64. 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(10):5424-5432.
65. Wang Y, Kelly CG, Karttunen JT, Whittall T, Lehner PJ, Duncan L, MacAry P, Younson JS, Singh M, Oehlmann W, Cheng G et al: CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity (2001) 15(6):971-983. • Differences between mammalian- and bacteria-derived Hsp70 suggested that small differences in structure could determine which Hsp receptors are utilized.
66. Becker T, Hartl FU, Wieland F: CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol (2002) 158(7):1277-1285.
67. Millar DG, Garza KM, Odermatt B, Elford AR, Ono N, Li Z, Ohashi PS: Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo. Nat Med (2003) 9(12):1469-1476.
68. Lazarevic V, Myers AJ, Scanga CA, Flynn JL: CD40, but not CD40L, is required for the optimal priming of T cells and control of aerosol M. tuberculosis infection. Immunity (2003) 19(6):823-835.
69. van Kooten C, Banchereau J: CD40-CD40 ligand. J Leukocyte Biol (2000) 67(1):2-17.
70. Berwin B, Hart JP, Rice S, Gass C, Pizzo SV, Post SR, Nicchitta CV: Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells. EMBO J (2003) 22(22):6127-6136.
71. Haworth R, Platt N, Keshav S, Hughes D, Darley E, Suzuki H, Kurihara Y, Kodama T, Gordon S: The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal endotoxic shock. J Exp Med (1997) 186(9):1431-1439.
72. Tewalt EF, Maynard JC, Walters JJ, Schell AM, Berwin BL, Nicchitta CV, Norbury CC: Redundancy renders the glycoprotein 96 receptor scavenger receptor A dispensable for cross priming in vivo. Immunology (2008):doi 10.1111/j.1365-2567.2008.02861.x.
73. Berwin B, Delneste Y, Lovingood RV, Post SR, Pizzo SV: SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin. J Biol Chem (2004) 279(49):51250-51257.
74. Rechner C, Kühlewein C, Müller A, Schild H, Rudel T: Host glycoprotein gp96 and scavenger receptor SREC interact with PorB of disseminating Neisseria gonorrhoeae in an epithelial invasion pathway. Cell Host Microbe (2007) 2(6):393-403.
75. Janetzki S, Palla D, Rosenhauer V, Lochs H, Lewis JJ, Srivastava PK: Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations: A pilot study. Int J Cancer (2000) 88(2):232-238.
76. Amato RJ, Murray L, Wood L, Savary C. Tomasovic S, Reitsma D: Active specific immunotherapy in patients with renal cell carcinoma (RCC) using autologous tumor derived heat shock protein-peptide complex-96 (HspP-96) vaccine. Proc Am Soc Clin Oncol (1999) 35:Abs 1278
77. Rivoltini L, Castelli C, Carrabba M, Mazzaferro V, Pilla L, Huber V, Coppa J, Gallino G, Scheibenbogen C, Squarcina P, Cova A et al: 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(7):3467-3474.
78. Mazzaferro V, Coppa J, Carrabba MG, Rivoltini L, Schiavo M, Regalia E, Mariani L, Camerini T, Marchianò A, Andreola S, Camerini R et al: Vaccination with autologous tumor-derived heat shock protein gp96 after liver resection for metastatic colorectal cancer. Clin Cancer Res (2003) 9(9):3235-3245.
79. Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, Gallino G, Piris A, Cattelan A, Lazzari I, Carrabba M et al: Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes. J Clin Oncol (2002) 20(20):4169-4180.
80. Testori A, Richards J, Whitman E, Mann GB, Lutzky J, Camacho L, Parmiani G, Tosti G, Kirkwood JM, Hoos A, Yuh L et al: 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(6):955-962.
81. Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F, Isakov L et al: 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, for the C-100-12 RCC Study Group. The Lancet (2008) 372(9633):145-154.
82. Kumaraguru U, Suvas S, Biswas PS, Azkur AK, Rouse BT. Concomitant helper response rescues otherwise low avidity CD8+ memory CTLs to become efficient effectors in vivo. J Immunol (2004) 172(6):3719-3724.
83. Hilf N, Singh-Jasuja H, Schwarzmaier P, Gouttefangeas C, Rammensee HG, Schild H: Human platelets express heat shock protein receptors and regulate dendritic cell maturation. Blood (2002) 99(10):3676-3682.
84. Breloer M, Fleischer B, von Bonin A: In vivo and in vitro activation of T cells after administration of Ag-negative heat shock proteins. J Immunol (1999) 162(6):3141-3147.
85. Multhoff G, Mizzen L, Winchester CC, Milner CM, Wenk S, Eissner G, Kampinga HH, Laumbacher B, Johnson J: Heat shock protein 70 (Hsp70) stimulates proliferation and cytolytic activity of natural killer cells. Exp Hematol (1999) 27(11):1627-1636.
86. Floto RA, MacAry PA, Boname JM, Mien TS, Kampmann B, Hair JR, Huey OS, Houben EN, Pieters J, Day C, Oehlmann W et al: Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5. Science (2006) 314(5798):454-458.