Peptide-based approaches to treat lupus and other autoimmune diseases

Journal of Autoimmunity

Volumn 39, Issue 3, 2012, Pages 143-153

  Schall, Nicolas ^a   Page, Nicolas ^a,b   Macri, Christophe ^a   Chaloin, Olivier ^a   Briand, Jean Paul ^a   Muller, Sylviane ^a  

^a INSTITUT DE BIOLOGIE MOLÉCULAIRE ET CELLULAIRE   (France)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

Altered peptide ligand; Excipient; P140 peptide; Systemic lupus erythematosus; Therapeutic peptides

Indexed keywords

15 MER PCONS PEPTIDE; 19 MER PEPTIDE; 21 MER PEPTIDE P140; CHOLERA TOXIN B SUBUNIT; DELMITIDE; DNAJP1 PEPTIDE; FORIGERIMOD; GLATIRAMER; HEAT SHOCK PROTEIN 60 PEPTIDE 336 351; HEPATITIS B CORE ANTIGEN; IL 23 9 MER PEPTIDE; IMMUNOSUPPRESSIVE AGENT; KEYHOLE LIMPET HEMOCYANIN; MBP PEPTIDE 83 99; P140 PEPTIDE; PLACEBO; RECOMBINANT CHOLERA TOXIN B; U1 70K PEPTIDE; UNCLASSIFIED DRUG;

ALLERGIC ENCEPHALOMYELITIS; ARTHRITIS; AUTOIMMUNE DISEASE; HUMAN; LUPUS VULGARIS; MULTIPLE SCLEROSIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; ULCERATIVE COLITIS; UVEITIS;

AMINO ACID SEQUENCE; ANIMALS; AUTOIMMUNE DISEASES; AUTOIMMUNITY; BIOLOGICAL AVAILABILITY; CLINICAL TRIALS AS TOPIC; DRUG ADMINISTRATION ROUTES; DRUG ADMINISTRATION SCHEDULE; HUMANS; IMMUNOLOGIC FACTORS; LUPUS ERYTHEMATOSUS, SYSTEMIC; MICE; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; SURVIVAL RATE;

EID: 84865390207     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2012.05.016     Document Type: Review

References (128)

1. Merrill J.T., Erkan D., Byon J.P. Challenge in bringing the bench to bedside in drug development for SLE. Nature Rev Drug Discov 2004, 3:1036-1046.
2. Larché M., Wraith D.C. Peptide-based therapeutic vaccines for allergic and autoimmune diseases. Nat Med 2005, 11:S69-S75.
3. Zompra A.A., Galanis A.S., Werbitzky O., Albericio F. Manufacturing peptides as active pharmaceutical ingredients. Future Med Chem 2009, 1:361-377.
4. Vlieghe P., Lisowski V., Martinez J., Khrestchatisky M. Synthetic therapeutic peptides: science and market. Drug Discov Today 2010, 15:40-56.
5. Fauchère J.L., Thurieau C. Evaluation of the stability of peptides and pseudopeptides as a tool in peptide drug design. Adv Drug Res 1992, 23:127-159.
6. Allen S.D., Rawale S.V., Whitacre C.C., Kaumaya P.T. Therapeutic peptidomimetic strategies for autoimmune diseases: costimulation blockade. J Pept Res 2005, 65:591-604.
7. Gentilucci L., De Marco R., Cerisoli L. Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization. Curr Pharm Des 2010, 16:3185-3203.
8. Briand J.P., Muller S. Synthetic peptides for the analysis of B-cell epitopes in autoantigens (chapter 9) in autoantibodies and autoimmunity: molecular mechanisms in health and disease 2005, 189-224. Wiley-VCH, Weinheim, Germany. K.M. Pollard (Ed.).
9. Briand J.P., Muller S. Emerging peptide therapeutics for inflammatory autoimmune diseases. Curr Pharm Des 2010, 16:1136-1142.
10. Harrison L.C., Hafler D.A. Antigen-specific therapy for autoimmune disease. Curr Opin Immunol 2000, 12:704-711.
11. Partidos C.D., Beignon A.S., Semetey V., Briand J.P., Muller S. The bare skin and the nose as non-invasive routes for administering peptide vaccines. Vaccine 2001, 19:2708-2715.
12. Partidos C.D., Muller S. Decision making at the surface of the intact or barrier disrupted skin: potential applications for vaccination or therapy. Cell Mol Life Sci 2005, 62:1418-1424.
13. Monneaux F., Muller S. Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects. Arthritis Res Ther 2009, 11:234.
14. Sabatos-Peyton C.A., Verhagen J., Wraith D.C. Antigen-specific immunotherapy of autoimmune and allergic diseases. Curr Opin Immunol 2010, 22:609-615.
15. Steinman L., Merrill J.T., McInnes I.B., Peakman M. Optimization of current and future therapy for autoimmune diseases. Nat Med 2012, 18:59-65.
16. Perretti M., Gavins F.N. Annexin 1: an endogenous anti-inflammatory protein. News Physiol Sci 2003, 18:60-64.
17. Zagury D., Burny A., Gallo R.C. Toward a new generation of vaccines: the anti-cytokine therapeutic vaccines. Proc Natl Acad Sci U S A 2001, 98:8024-8029.
18. Le Buanec H., Delavallée L., Bessis N., Paturance S., Bizzini B., Gallo R., et al. TNFα kinoid vaccination-induced neutralizing antibodies to TNFα protects mice from autologous TNFα-driven chronic and acute inflammation. Proc Natl Acad Sci U S A 2006, 103:19442-19447.
19. Bertin-Maghit S.M., Capini C.J., Bessis N., Chomilier J., Muller S., Rappaport J., et al. Active immunization against murine IL-1β peptides protects against collagen-induced arthritis. Vaccine 2005, 23:4228-4235.
20. Guan Q., Ma Y., Hillman C.L., Qing G., Ma A.G., Weiss C.R., et al. Targeting IL-12/IL-23 by employing a p40 peptide-based vaccine ameliorates TNBS-induced acute and chronic murine colitis. Mol Med 2011, 17:646-656.
21. Ratsimandresy R.A., Duvallet E., Assier E., Semerano L., Delavallée L., Bessis N., et al. Active immunization against IL-23p19 improves experimental arthritis. Vaccine 2011, 29:9329-9336.
22. Ma Y., Ma A.G., Peng Z. A potential immunotherapy approach: mucosal immunization with an IL-13 peptide-based virus-like particle vaccine in a mouse asthma model. Vaccine 2007, 25:8091-8099.
23. Semerano L., Assier E., Delavallée L., Boissier M.C. Kinoid of human tumor necrosis factor-alpha for rheumatoid arthritis. Expert Opin Biol Ther 2011, 11:545-550.
24. Hahn B.H., Singh R.R., Wong W.K., Tsao B.P., Bulpitt K., Ebling F.M. Treatment with a consensus peptide based on amino acid sequences in autoantibodies prevents T cell activation by autoantigens and delays disease onset in murine lupus. Arthritis Rheum 2001, 44:432-441.
25. Singh R.P., La Cava A., Wong M., Ebling F., Hahn B.H. CD8+ T cell-mediated suppression of autoimmunity in a murine lupus model of peptide-induced immune tolerance depends on Foxp3 expression. J Immunol 2007, 178:7649-7657.
26. Zinger H., Eilat E., Meshorer A., Mozes E. Peptides based on the complementarity-determining regions of a pathogenic autoantibody mitigate lupus manifestations of (NZB x NZW)F1 mice via active suppression. Int Immunol 2003, 15:205-214.
27. Elmann A., Sharabi A., Dayan M., Zinger H., Ophir R., Mozes E. Altered gene expression in mice with lupus treated with edratide, a peptide that ameliorates the disease manifestations. Arthritis Rheum 2007, 56:2371-2381.
28. Sharabi A., Mozes E. The suppression of murine lupus by a tolerogenic peptide involves Foxp3-expressing CD8 cells that are required for the optimal induction and function of Foxp3-expressing CD4 cells. J Immunol 2008, 181:3243-3251.
29. Sela U., Sharabi A., Dayan M., Hershkoviz R., Mozes E. The role of dendritic cells in the mechanism of action of a peptide that ameliorates lupus in murine models. Immunology 2009, 128(1 Suppl):e395-e405.
30. Hahn B.H., Anderson M., Le E., La Cava A. Anti-DNA Ig peptides promote Treg cell activity in systemic lupus erythematosus patients. Arthritis Rheum 2008, 58:2488-2497.
31. Sthoeger Z.M., Sharabi A., Dayan M., Zinger H., Asher I., Sela U., et al. The tolerogenic peptide, hCDR1, down-regulates pathogenic cytokines and apoptosis and up-regulates immunosuppressive molecules and regulatory T cells in peripheral blood mononuclear cells of lupus patients. Hum Immunol 2009, 70:139-145.
32. Kaliyaperumal A., Michaels M.A., Datta S.K. Antigen-specific therapy of murine lupus nephritis using nucleosomal peptides: tolerance spreading impairs pathogenic function of autoimmune T and B cells. J Immunol 1999, 162:5775-5783.
33. Wu H.Y., Ward F.J., Staines N.A. Histone peptide-induced nasal tolerance: suppression of murine lupus. J Immunol 2002, 169:1126-1134.
34. Wu H.Y., Staines N.A. A deficiency of CD4+CD25+ T cells permits the development of spontaneous lupus-like disease in mice, and can be reversed by induction of mucosal tolerance to histone peptide autoantigen. Lupus 2004, 13:192-200.
35. Kang H.K., Michaels M.A., Berner B.R., Datta S.K. Very low-dose tolerance with nucleosomal peptides controls lupus and induces potent regulatory T cell subsets. J Immunol 2005, 174:3247-3255.
36. Suen J.L., Chuang Y.H., Tsai B.Y., Yau P.M., Chiang B.L. Treatment of murine lupus using nucleosomal T cell epitopes identified by bone marrow-derived dendritic cells. Arthritis Rheum 2004, 50:3250-3259.
37. Mihaylova N., Voynova E., Tchorbanov A., Nikolova M., Michova A., Todorov T., et al. Selective silencing of disease-associated B-lymphocytes by chimeric molecules targeting their Fc gamma IIb receptor. Int Immunol 2008, 20:165-175.
38. Amital H., Heilweil M., Ulmansky R., Szafer F., Bar-Tana R., Morel L., et al. Treatment with a laminin-derived peptide suppresses lupus nephritis. J Immunol 2005, 175:5516-5523.
39. Daniel D., Wegmann D.R. Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23). Proc Natl Acad Sci U S A 1996, 93:956-960.
40. Hutchings P., Cooke A. Protection from insulin dependent diabetes mellitus afforded by insulin antigens in incomplete Freund's adjuvant depends on route of administration. J Autoimmun 1998, 11:127-130.
41. Alleva D.G., Gaur A., Jin L., Wegmann D., Gottlieb P.A., Pahuja A., et al. Immunological characterization and therapeutic activity of an altered-peptide ligand, NBI-6024, based on the immunodominant type 1 diabetes autoantigen insulin B-chain (9-23) peptide. Diabetes 2002, 51:2126-2134.
42. Kobayashi M., Abiru N., Arakawa T., Fukushima K., Zhou H., Kawasaki E., et al. Altered B:9-23 insulin, when administered intranasally with cholera toxin adjuvant, suppresses the expression of insulin autoantibodies and prevents diabetes. J Immunol 2007, 179:2082-2088.
43. Elias D., Reshef T., Birk O.S., van der Zee R., Walker M.D., Cohen I.R. Vaccination against autoimmune mouse diabetes with a T-cell epitope of the human 65-kDa heat shock protein. Proc Natl Acad Sci U S A 1991, 88:3088-3091.
44. Ablamunits V., Elias D., Reshef T., Cohen I.R. 15. Islet T cells secreting IFN-gamma in NOD mouse diabetes: arrest by p277 peptide treatment. J Autoimmun 1998, 11:73-81.
45. Delaleu N., Madureira A.C., Immervoll H., Jonsson R. Inhibition of experimental Sjögren's syndrome through immunization with HSP60 and its peptide amino acids 437-460. Arthritis Rheum 2008, 58:2318-2328.
46. Jin L., Zhu A., Wang Y., Chen Q., Xiong Q., Li J., et al. A Th1-recognized peptide P277, when tandemly repeated, enhances a Th2 immune response toward effective vaccines against autoimmune diabetes in nonobese diabetic mice. J Immunol 2008, 180:58-63.
47. Raz I., Elias D., Avron A., Tamir M., Metzger M., Cohen I.R. Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial. Lancet 2001, 358:1749-1753.
48. Huurman V.A.L., Decochez K., Mathieu C., Cohen I.R., Roep B.O. Therapy with the hsp60 peptide DiaPep277™ in C-peptide positive type 1 diabetes patients. Diabetes Metab Res Rev 2007, 23:269-275.
49. Huurman V.A., van der Meide P.E., Duinkerken G., Willemen S., Cohen I.R., Elias D., et al. Immunological efficacy of heat shock protein 60 peptide DiaPep277 therapy in clinical type I diabetes. Clin Exp Immunol 2008, 152:488-497.
50. Tuccinardi D., Fioriti E., Manfrini S., D'Amico E., Pozzilli P. DiaPep277 peptide therapy in the context of other immune intervention trials in type 1 diabetes. Expert Opin Biol Ther 2011, 11:1233-1240.
51. Stanford M., Whittall T., Bergmeier L.A., Lindblad M., Lundin S., Shinnick T., et al. Oral tolerization with peptide 336-351 linked to cholera toxin B subunit in preventing relapses of uveitis in Behcet's disease. Clin Exp Immunol 2004, 137:201-208.
52. Koffeman E.C., Genovese M., Amox D., Keogh E., Santana E., Matteson E.L., et al. Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial. Arthritis Rheum 2009, 60:3207-3216.
53. Evavold B.D., Sloan-Lancaster J., Allen P.M. Tickling the TCR: selective T-cell functions stimulated by altered peptide ligands. Immun Today 1993, 14:602-609.
54. Germain R.N. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell 1994, 76:287-299.
55. Madrenas J., Wange R.L., Wang J.L., Isakov N., Samelson L.E., Germain R.N. Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science 1995, 267:515-518.
56. England R.D., Kullberg M.C., Cornette J.L., Berzofsky J.A. Molecular analysis of a heteroclitic T cell response to the immunodominant epitope of sperm whale myoglobin. Implications for peptide partial agonists. J Immunol 1995, 155:4295-4306.
57. Kersh G.J., Allen P.M. Structural basis for T cell recognition of altered peptide ligands: a single T cell receptor can productively recognize a large continuum of related ligands. J Exp Med 1996, 184:1259-1268.
58. Rabinowitz J.D., Beeson C., Wülfing C., Tate K., Allen P.M., Davis M.M., et al. Altered T cell receptor ligands trigger a subset of early T cell signals. Immunity 1996, 5:125-135.
59. Ostankovitch M., Guichard G., Connan F., Muller S., Chaboissier A., Hoebeke J., et al. A partially modified retro-inverso pseudopeptide modulates the cytokine profile of CTL specific for an influenza virus epitope. J Immunol 1998, 161:200-208.
60. Chau L.A., Bluestone J.A., Madrenas J. Dissociation of intracellular signaling pathways in response to partial agonist ligands of the T cell receptor. J Exp Med 1998, 187:1699-1709.
61. Grossman Z., Paul W.E. Autoreactivity, dynamic tuning and selectivity. Curr Opin Immunol 2001, 13:687-698.
62. Jones D.S., Reichardt P., Ford M.L., Edwards L.J., Evavold B.D. TCR antagonism by peptide requires high TCR expression. J Immunol 2008, 181:1760-1766.
63. Fairchild P.J. Altered peptide ligands: prospects for immune intervention in autoimmune disease. Eur J Immunogenet 1997, 24:155-167.
64. Anderton S.M. Peptide-based immunotherapy of autoimmunity: a path of puzzles, paradoxes and possibilities. Immunology 2001, 104:367-376.
65. Alacaro M.C., Papini A.M. Contribution of peptides to multiple sclerosis research. Biopolymers 2006, 84:349-367.
66. Marino M., Ippolito A., Fassina G. Inhibition of experimental autoimmune encephalomyelitis in SJL mice by oral administration of retro-inverso derivative of encephalitogenic epitope P87-99. Eur J Immunol 1999, 29:2560-2566.
67. Chorev M., Goodman M. Recent developments in retro peptides and proteins - an ongoing topochemical exploration. Trends Biotechnol 1995, 13:438-445.
68. Guichard G., Benkirane N., Zeder-Lutz G., Van Regenmortel M.H.V., Briand J.P., Muller S. Antigenic mimicry of natural L-peptides with retro-inverso peptidomimetics. Proc Natl Acad Sci U S A 1994, 91:9765-9769.
69. Samson M.F., Smilek D.E. Reversal of acute experimental autoimmune encephalomyelitis and prevention of relapses by treatment with a myelin basic protein peptide analogue modified to form long-lived peptide-MHC complexes. J Immunol 1995, 155:2737-2746.
70. Margot C.D., Ford M.L., Evavold B.D. Amelioration of established experimental autoimmune encephalomyelitis by an MHC anchor-substituted variant of proteolipid protein 139-151. J Immunol 2005, 174:3352-3358.
71. Iwanami K., Matsumoto I., Yoshiga Y., Inoue A., Kondo Y., Yamamoto K., et al. Altered peptide ligands inhibit arthritis induced by glucose-6-phosphate isomerase peptide. Arthritis Res Ther 2009, 11:R167.
72. Bielekova B., Goodwin B., Richert N., Cortese I., Kondo T., Afshar G., et al. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med 2000, 6:1167-1175.
73. Kappos L., Comi G., Panitch H., Oger J., Antel J., Conlon P., et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. Nat Med 2000, 6:1176-1182. The Altered Peptide Ligand in Relapsing MS Study Group.
74. Travis S., Yap L.M., Hawkey C., Warren B., Lazarov M., Fong T., RDP Investigators Study Group, et al. RDP58 is a novel and potentially effective oral therapy for ulcerative colitis. Inflamm Bowel Dis 2005, 11:713-719.
75. Teitelbaum D., Meshorer A., Hirshfeld T., Arnon R., Sela M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur J Immunol 1971, 1:242-248.
76. Johnson K.P., Brooks B.R., Cohen J.A., Ford C.C., Goldstein J., Lisak R.P., et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. Neurology 1995, 45:1268-1276. The Copolymer 1 Multiple Sclerosis Study Group.
77. Johnson K.P., Due D.L. Benefits of glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis. Expert Rev Pharmacoecon Outcomes Res 2009, 9:205-214.
78. Vieira P.L., Heystek H.C., Wormmeester J., Wierenga E.A., Kapsenberg M.L. Glatiramer acetate (copolymer-1, copaxone) promotes Th2 cell development and increased IL-10 production through modulation of dendritic cells. J Immunol 2003, 170:4483-4488.
79. Weber M.S., Hohlfeld R., Zamvil S.S. Mechanism of action of glatiramer acetate in treatment of multiple sclerosis. Neurotherapeutics 2007, 4:647-653.
80. Borel P., Benkhoucha M., Weber M.S., Zamvil S.S., Santiago-Raber M.L., Lalive P.H. Glatiramer acetate treatment does not modify the clinical course of (NZB x BXSB)F1 lupus murine model. Int Immunol 2008, 20:1313-1319.
81. Greidinger E.L., Foecking M.F., Schafermeyer K.R., Bailey C.W., Primm S.L., Lee D.R., et al. T cell immunity in connective tissue disease patients targets the RNA binding domain of the U1-70kDa small nuclear ribonucleoprotein. J Immunol 2002, 169:3429-3437.
82. Hof D., Raats J.M., Pruijn G.J. Apoptotic modifications affect the autoreactivity of the U1 snRNP autoantigen. Autoimmun Rev 2005, 4:380-388.
83. Kattah N.H., Kattah M.G., Utz P.J. The U1-snRNP complex: structural properties relating to autoimmune pathogenesis in rheumatic diseases. Immunol Rev 2010, 233:126-145.
84. Monneaux F., Briand J.-P., Muller S. B and T cell immune response to small nuclear ribonucleoprotein particles in lupus mice: autoreactive CD4(+) T cells recognize a T cell epitope located within the RNP80 motif of the 70K protein. Eur J Immunol 2000, 30:2191-2200.
85. Monneaux F., Dumortier H., Steiner G., Briand J.P., Muller S. Murine models of systemic lupus erythematosus: B and T cell responses to spliceosomal ribonucleoproteins in MRL/Faslpr and (NZBxNZW)F1 lupus mice. Intern Immunol 2001, 13:1155-1163.
86. Monneaux F., Lozano J.M., Patarroyo M.E., Briand J.P., Muller S. T cell recognition and therapeutic effects of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MRL/lpr lupus mice. Eur J Immunol 2003, 33:287-296.
87. Monneaux F., Hoebeke J., Sordet C., Nonn C., Briand J.P., Maillère B., et al. Selective modulation of CD4+ T cells from lupus patients by a promiscuous, protective peptide analogue. J Immunol 2005, 175:5839-5847.
88. Page N., Gros F., Schall N., Décossas M., Bagnard D., Briand J.P., Muller S. HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus. Ann Rheum Dis 2011, 70:837-843.
89. Page N., Schall N., Strub J.M., Quinternet M., Chaloin O., Décossas M., et al. The spliceosomal phosphopeptide P140 controls the lupus disease by interacting with the HSC70 protein and via a mechanism mediated by γδ T cells. PloS ONE 2009, 4:e5273.
90. Monneaux F., Parietti V., Briand J.P., Muller S. Importance of spliceosomal RNP1 motif for intermolecular T-B cell spreading and tolerance restoration in lupus. Arthritis Res Ther 2007, 9:R111.
91. Dieker J., Cisterna B., Monneaux F., Décossas M., van der Vlag J., Biggiogera M., et al. Apoptosis changes the phosphorylation status and subcellular localization of the spliceosomal autoantigen U1-70K. Cell Death Diff 2008, 15:793-804.
92. Woppmann A., Will C.L., Kornstädt U., Zuo P., Manley J.L., Lürhrmann R. Identification of an snRNP-associated kinase activity that phosphorylates arginine/serine rich domains typical of splicing factors. Nuc Acids Res 1993, 21:2815-2822.
93. Young J.C., Agashe V.R., Siegers K., Hartl F.U. Pathways of chaperone-mediated protein folding in the cytosol. Nat Rev Cell Biol 2004, 5:781-791.
94. Mayer M.P., Bukau B. Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 2005, 62:670-684.
95. Daugaard M., Rohde M., Jäättelä M. The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett 2007, 581:3702-3710.
96. Kampinga H.H., Craig E.A. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Molec Cell Biol 2010, 11:579-592.
97. Schick C., Arbogast M., Lowka K., Rzepka R., Melchers I. Continuous enhanced expression of Hsc70 but not Hsp70 in rheumatoid arthritis synovial tissue. Arthritis Rheum 2004, 50:88-93.
98. Auger I., Escola J.M., Gorvel J.P., Roudier J. HLA-DR4 and HLA-DR10 motifs that carry susceptibility to rheumatoid arthritis bind 70-kD heat shock proteins. Nat Med 1996, 2:306-310.
99. Panjwani N., Akbari O., Garcia S., Brazil M., Stockinger B. The HSC73 molecular chaperone: involvement in MHC class II antigen presentation. J Immunol 1999, 163:1936-1942.
100. Majeski A.E., Dice J.F. Mechanisms of chaperone-mediated autophagy. Int J Biochem Cell Biol 2004, 36:2435-2444.
101. Arndt V., Dick N., Tawo R., Dreiseidler M., Wenzel D., Hesse M., et al. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol 2010, 20:143-148.
102. Crotzer V.L., Blum J.S. Autophagy and its role in MHC-mediated antigen presentation. J Immunol 2009, 182:3335-3341.
103. Kon M., Cuervo A.M. Chaperone-mediated autophagy in health and disease. FEBS Let 2010, 584:1399-1401.
104. Bejarano E., Cuervo A.M. Chaperone-mediated autophagy. Proc Am Thorac Soc 2010, 7:29-39.
105. Li W., Yang Q., Mao Z. Chaperone-mediated autophagy: machinery, regulation and biological consequences. Cell Mol Life Sci 2011, 68:749-763.
106. Dani A., Chaudhry A., Mukherjee P., Rajagopal D., Bhatia S., George A., et al. The pathway for MHCII-mediated presentation of endogeneous proteins involves peptide transport to the endo-lysosomal compartment. J Cell Sci 2004, 117:4219-4230.
107. Paludan C., Schmid D., Landthaler M., Vockerodt M., Kube D., Tuschl T., et al. Endogeneous MHCII processing of a viral nuclear antigen after autophagy. Science 2005, 307:593-596.
108. Lleo A., Invernizzi P., Selmi C., Coppel R.L., Alpini G., Podda M., et al. Autophagy: highlighting a novel player in the autoimmunity scenario. J Autoim 2007, 29:61-68.
109. Nedjic J., Aichinger M., Emmercich J., Mizushima N., Klein L. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 2008, 455:396-400.
110. Münz C. Enhancing immunity through autophagy. Annu Rev Immunol 2009, 27:423-449.
111. Klein L., Münz C., Lünemann J.D. Autophagy-mediated antigen processing in CD4(+) T cell tolerance and immunity. FEBS Lett 2010, 584:1405-1410.
112. Page N., Gros F., Schall N., Briand J.P., Muller S. A therapeutic peptide in lupus alters autophagic processes and stability of MHCII molecules in MRL/lpr B cells. Autophagy 2011, 7:539-540.
113. Mizushima N., Yoshimori T., Levine B. Methods in mammalian autophagy research. Cell 2010, 140:313-326.
114. Monneaux F., Parietti V., Briand J.P., Muller S. Intramolecular T cell spreading in unprimed MRL/lpr mice: importance of the U1-70K protein sequence 131-151. Arthritis Rheum 2004, 50:3232-3238.
115. Dali H., Busnel O., Hoebeke J., Bi L., Decker P., Briand J.P., et al. Heteroclitic properties of mixed alpha- and aza-beta3-peptides mimicking a supradominant CD4 T cell epitope presented by nucleosome. Mol Immunol 2007, 44:3024-3036.
116. Mézière C., Viguier M., Dumortier H., Lo-Man R., Leclerc C., Guillet J.G., et al. In vivo T-helper cell response to retro-inverso peptidomimetics. J Immunol 1997, 159:3230-3237.
117. Srivastava P. Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2002, 2:185-194.
118. Freeman B.C., Myers M.P., Schumacher R., Morimoto R.I. Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1. EMBO J 1995, 14:2281-2292.
119. Muller S., Monneaux F., Schall N., Rashkov R.K., Oparanov B.A., Wiesel P., et al. Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus. Results of an early phase II clinical trial. Arthritis Rheum 2008, 58:3873-3883.
120. Gordon C., Sutcliffe N., Skan J., Stoll T., Isenberg D.A. Definition and treatment of lupus flares measured by the BILAG index. Rheumatology 2003, 42:1372-1379.
121. Gros F, Arnold J, Page N, Décossas M, Korganow AS, Martin T, et al. Macroautophagy is deregulated in murine and human lupus T lymphocytes. Autophagy, in press.
122. Sarkar S., Davies J.E., Huang Z., Tunnacliffe A., Rubinsztein D.C. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem 2007, 282:5641-5652.
123. Aguib Y., Heiseke A., Gilch S., Riemer C., Baier M., Schätzl H.M., et al. Autophagy induction by trehalose counteracts cellular prion infection. Autophagy 2009, 5:361-369.
124. Renna M., Jimenez-Sanchez M., Sarkar S., Rubinsztein D.C. Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases. J Biol Chem 2010, 285:11061-11067.
125. Mackay I.R., Leskovsek N.V., Rose N.R. The odd couple: a fresh look at autoimmunity and immunodeficiency. J Autoimmun 2010, 35:199-205.
126. Youinou P., Moutsopoulos H.M. A lifetime in autoimmunity. J Autoimmun 2010, 35:171-175.
127. Gershwin M.E., Shoenfeld Y., David C. A lifetime contribution in translational immunology. J Autoimmun 2011, 37:59-62.
128. Rose N.R. The genetics of autoimmune thyroiditis: the first decade. J Autoimmun 2011, 37:88-94.