T-cell-based immunotherapy in multiple sclerosis: Induction of regulatory immune networks by T-cell vaccination

Expert Review of Clinical Immunology

Volumn 2, Issue 5, 2006, Pages 705-716

  Hellings, Niels ^a   Raus, Jef ^a   Stinissen, Piet ^a  

^a HASSELT UNIVERSITY   (Belgium)

Author keywords

Anticlonotypic; Antiergotypic T cells; Autoreactive T cells; Qa 1 dependent T cells; Regulatory networks; T cells; T cell vaccination

Indexed keywords

EID: 47049091644     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1586/1744666X.2.5.705     Document Type: Review

References (112)

1. Ffrench-Constant C. Pathogenesis of multiple sclerosis. Lancet 343, 271-275 (1994). (Pubitemid 24039632)
2. Hellings N, Raus J, Stinissen V. Insights into the immunopathogenesis of multiple sclerosis. Immunol. Res. 25, 27-51 (2002). (Pubitemid 34155248)
3. Zhang J, Medaer R, Hashim GA, Chin Y, van den Berg-Loonen E, Raus J. Myelin basic protein-specific T lymphocytes in multiple sclerosis and controls: precursor frequency, fine specificity, and cytotoxicity. Ann. Neurol. 32, 330-338 (1992).
4. Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA. T cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346, 183-187 (1990).
5. Pette M, Fujita K, Wilkinson D et al. Myelin autoreactivity in multiple sclerosis: recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors. Proc. Natl Acad. Sci. USA 87, 7968-7972 (1990).
6. Martin R, Howell MD, Jaraquemada D et al A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis, J. Exp. Med. 173, 19-24 (1991).
7. Chou YK, Bourdette DN, Offner H et al. Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis, J. Neuroimmunol. 38, 105-113(1992).
8. Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA. Increased frequency of interleukin 2-responsiveT cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J. Exp. Med. 179, 973-984(1994). (Pubitemid 24065655)
9. Lee SJ, Wucherpfennig KW, Brod SA, Benjamin D, Weiner HL, Hafler DA. Common T cell receptor V β usage in oligoclonal T lymphocytes derived from cerebrospinal fluid and blood of patients with multiple sclerosis. Ann. Neurol. 29, 33-40 (1991).
10. Hafler DA, Duby AD, Lee SJ, Benjamin D, Seidman JG, Weiner HL. Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis. J. Exp. Med. 167, 1313-1322(1988).
11. Oksenberg JR, Panzara MA, Begovich AB et al. Selection for T cell receptor V β-D β-J β gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature 362, 68-70(1993). (Pubitemid 23087292)
12. Allegretta M, Albertini RJ, Howell MD et al. Homologies between T cell receptor junctional sequences unique to multiple sclerosis and T cells mediating experimental allergic encephalomyelitis. J. Clin. Invest. 94, 105-109 (1994). (Pubitemid 24218082)
13. Kondo S, Shimizu A, Maeda M, Tagaya Y, Yodoi J, Honjo T. Expression of functional human interleukin-2 receptor in mouse T cells by cDNA transfection. Nature 320, 75-77 (1986). (Pubitemid 16105251)
14. Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA. T cell receptor V a-V β repertoire and cytokine gene expression in active multiple sclerosis lesions. J. Exp. Med. 175, 993-1002 (1992).
15. Sun JB, Olsson T, Wang WZ et al. Autoreactive T and B cells responding to myelin proteolipid protein in multiple sclerosis and controls. Eur. J. Immunol. 21, 1461-1468(1991).
16. Trotter JL, Damico CA, Cross AH et al. HPRT mutant T cell lines from multiple sclerosis patients recognize myelin proteolipid protein peptides. J. Neuroimmunol. 75, 95-103 (1997). (Pubitemid 27170307)
17. Allegretta M, Nicklas JA, Sriram S, Albertini RJ. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 247, 718-721 (1990).
18. Wucherpfennig KW, Zhang J, Witek C et al. Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. J. Immunol. 152, 5581-5592 (1994). (Pubitemid 24153008)
19. Vandevyver C, Mertens N, van den Eisen P, Medaer R, Raus J, Zhang J. Clonal expansion of myelin basic protein-reactive T cells in patients with multiple sclerosis: restricted T cell receptor V gene rearrangements and CDR3 sequence. Eur. J. Immunol. 25, 958-968 (1995).
20. Goebels N, Hofstetter H, Schmidt S, Brunner C, Wekerle H, Hohlfeld R. Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence. Brain 123(Pt 3), 508-518 (2000). (Pubitemid 30099536)
21. Hafler DA, Saadeh MG, Kuchroo VK, Milford E, Steinman L. TCR usage in human and experimental demyelinating disease. Immunol. Today 17, 152-159 (1996). (Pubitemid 26113082)
22. Van der Aa A, Hellings N, Bernard CCA, Raus J, Stinissen P. Functional properties of myelin oligodendrocyte glycoprotein-reactive T cells in multiple sclerosis patients and controls. J. NeuroimmunoL 137, 164-176(2003). (Pubitemid 36351579)
23. Markovic-Plese S, Cortese I, Wandinger KP, McFarland HF, Martin R. CD4(+)CD28(-) costimulation-independent T cells in multiple sclerosis. J. Clin. Invest. 108, 1185-1194(2001). (Pubitemid 32995377)
24. Lovett-Racke AE, Trotter JL, Lauber J, Perrin PJ, June CH, Racke MK. Decreased dependence of myelin basic protein-reactive T cells on CD28-mediated costimulation in multiple sclerosis patients. A marker of activated/memory T cells. J. Clin. Invest. 101, 725-730(1998). (Pubitemid 28096067)
25. Scholz C, Patton KT, Anderson DE, Freeman GJ, Hafler DA. Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. J. Immunol 160, 1532-1538 (1998). (Pubitemid 28093458)
26. Bielekova B, Muraro PA, Golestaneh L, Pascal J, McFarland HF, Martin R. Preferential expansion of autoreactive T lymphocytes from the memory T cell pool by IL-7. J. NeuroimmunoL 100, 115-123(1999). (Pubitemid 30038245)
27. Bielekova B, Sung MH, Kadom N, Simon R, McFarland H, Martin R. Expansion and functional relevance of high-avidity myelin-specific CD4(+) T cells in multiple sclerosis. J. Immunol 172, 3893-3904 (2004). (Pubitemid 38337977)
28. Mandel M, Gurevich M, Lavie G, Cohen IR, Achiron A. Unique gene expression patterns in human T cell lines generated from multiple sclerosis patients by stimulation with a synthetic MOG peptide. Clin. Dev. Immunol 12, 203-209 (2005). (Pubitemid 43205645)
29. Cepok S, Zhou D, Srivastava R et al. Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis. J. Clin. Invest. 115, 1352-1360 (2005). (Pubitemid 40629055)
30. Somers V, Govarts C, Hellings N, Hupperts R, Stinissen P. Profiling the autoantibody repertoire by serological antigen selection. J. Autoimmun. 25, 223-228 (2005). (Pubitemid 41654467)
31. Zhao YD, Gran B, Pinilla C et al. Combinatorial peptide libraries and biométrie score matrices permit the quantitative analysis of specific and degenerate interactions between clonotypic TCR and MHC peptide ligands. J. Immunol. 167, 2130-2141 (2001). (Pubitemid 32747522)
32. Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47, 707-717 (2000). (Pubitemid 30390191)
33. Wolinsky JS. The PROMiSe trial: baseline data review and progress report. Mult. Scler. 10(Suppl. 1), S65-S71 (2004).
34. Rudick RA, Cutter G, Monika B et al. Estimating effects of disease modifying therapy in patients with multiple sclerosis followed longitudinally after a controlled clinical trial. Neurology. 56, A353-A354 (2001).
35. Noseworthy JH, Gold R, Härtung HP. Treatment of multiple sclerosis: recent trials and future perspectives. Curr. Opin. Neuro L 12, 279-293 (1999). (Pubitemid 29378162)
36. Muir M, Lovett-Racke AE, Racke MK. Novel therapeutic strategies targeting the pathogenic T cells in multiple sclerosis. Exp. Rev. Clin. Immunol. 1, 345-355 (2005).
37. Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80, 695-705 (1995).
38. Hemmer B, Vergelli M, Gran B et al. Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology. J. Immunol. 160, 3631-3636 (1998). (Pubitemid 28176061)
39. Cohen IR. The cognitive paradigm and the immunological homunculus. Immunol. Today 13, 490-494 (1992).
40. Ben Nun A, Wekerle H, Cohen IR. Vaccination against autoimmune encephalomyelitis with T-lymphocyte line cells reactive against myelin basic protein. Nature 292, 60-61 (1981). (Pubitemid 11048545)
41. Lider O, Reshef T, Beraud E, Ben Nun A, Cohen IR. Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. Science 239, 181-183 (1988). (Pubitemid 18026682)
42. Lider O, Beraud E, Reshef T, Friedman A, Cohen IR. Vaccination against experi-mental autoimmune encephalomyelitis using a subencephalitogenic dose of autoimmune effector T cells. (2). Induction of a protective anti-idiotypic response. J. Autoimmun. 2, 87-99(1989).
43. Lohse AW, Mor F, Karin N, Cohen IR. Control of experimental autoimmune encephalomyelitis by T cells responding to activated T cells. Science 244, 820-822 (1989). (Pubitemid 19163870)
44. Lohse AW, Spahn TW, Wolfel T, Herkei J, Cohen IR, Meyer zum Buschenfelde KH. Induction of the anti-ergotypic response. Int. Immunol 5, 533-539 (1993). (Pubitemid 23162522)
45. Medaer R, Stinissen P, Truyen L, Raus J, Zhang J. Depletion of myelin-basic-protein autoreactive T cells by T cell vaccination: pilot trial in multiple sclerosis. Lancet 346, 807-808 (1995).
46. Zhang J, Medaer R, Stinissen P, Hafler D, Raus J. MHC-restricted depletion of human myelin basic protein-reactive T cells by T cell vaccination. Science 261, 1451-1454 (1993). (Pubitemid 23334267)
47. Stinissen P, Zhang J, Medaer R, Vandevyver C, Raus J. Vaccination with autoreactive T cell clones in multiple sclerosis: overview of immunological and clinical data. J. Neurosti. Res. 45, 500-511 (1996). (Pubitemid 26299607)
48. Zhang J, Vandevyver C, Stinissen P, Raus J. In vivo clonotypic regulation of human myelin basic protein-reactive T cells by T cell vaccination. J. Immunol. 155, 5868-5877 (1995).
49. Hermans G, Denzer U, Lohse A, Raus J, Stinissen P. Cellular and humoral immune responses against autoreactive T cells in multiple sclerosis patients after T cell vaccination. J. Autoimmun. 13, 233-246 (1999). (Pubitemid 29436138)
50. Zhang JZ, Rivera VM, Tejada-Simon MV et al. T cell vaccination in multiple sclerosis: results of a preliminary study. J. Neurol. 249, 212-218 (2002). (Pubitemid 34143478)
51. Zhang YC, Hong J, Tejada-Simon MV et al. Th2 immune regulation induced by T cell vaccination in patients with multiple sclerosis. Eur. J. Immunol. 30, 908-913 (2000). (Pubitemid 30216265)
52. Correale J, Lund B, McMillan M, Ko DY, McCarthy K, Weiner LP. T cell vaccination in secondary progressive multiple sclerosis. J. Neuroimmunol. 107, 130-139 (2000). (Pubitemid 30347418)
53. Summarizes results of a TCV clinical trial in secondary progressive MS patients using bovine myelin-reactive T cell lines.
54. Achiron A, Lavie G, Kishner I et al. T cell vaccination in multiple sclerosis relapsing-remitting nonresponders patients. Clin. Immunol. 113, 155-160 (2004). (Pubitemid 39296848)
55. Elias D, Reshef T, Birk OS, Van Der ZR, Walker MD, Cohen IR. Vaccination against autoimmune mouse diabetes with a T cell epitope of the human 65-kDa heat shock protein. Proc. Natl Acad. Sci. USA 88, 3088-3091 (1991). (Pubitemid 21916564)
56. Holoshitz J, Naparstek Y, Ben Nun A, Cohen IR. Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science 219, 56-58(1983). (Pubitemid 13204148)
57. Kakimoto K, Katsuki M, Hirofuji T, Iwata H, Koga T. Isolation of T cell line capable of protecting mice against collagen-induced arthritis, J. Immunol. 140, 78-83 (1988). (Pubitemid 18050684)
58. Beraud E, Kotake S, Caspi RR et al. Control of experimental autoimmune uveoretinitis by low dose T cell vaccination. Cell Immunol. 140, 112-122 (1992).
59. Shapira OM, Mor E, Reshef T, Pfeffermann RA, Cohen IR. Prolongation of survival of rat cardiac allografts by T cell vaccination. J. Clin. Invest. 91, 388-390 (1993). (Pubitemid 23064117)
60. van Laar JM, Miltenburg AM, Verdonk MJ et al. Effects of inoculation with attenuated autologous T cells in patients with rheumatoid arthritis. J. Autoimmun. 6, 159-167 (1993). (Pubitemid 23161774)
61. Atlan H, Gersten MJ, Salk PL, Salk J. Can AIDS be prevented by T cell vaccination? Immunol. Today 14, 200-202 (1993). (Pubitemid 23124511)
62. Agnholt J, Kaltoft K, Jakobsen NO, Dahlerup JE T cell vaccination in Crohn's disease: principles and presentation of the first two cases. Cytokines Cell Mol. Ther. 7, 117-123(2002). (Pubitemid 36850426)
63. Li ZG, Mu R, Dai ZP, Gao XM. T cell vaccination in systemic lupus erythematosus with autologous activated T cells. Lupus 14, 884-889 (2005). (Pubitemid 41736369)
64. Cohen IR. The life and times of T cell vaccination. In: T Cell Vaccination and Autoimmune Disease. Zhang J, Raus J (Eds). R.G. Landes Co., TX, USA (1995).
65. Herkel J, Brunner S, Meyer zum Buschenfelde KH, Lohse AW. Humoral mechanisms in T cell vaccination: induction and functional characterization of anti-lymphocytic autoantibodies. J. Autoimmun. 10, 137-146 (1997). (Pubitemid 27242454)
66. Hermans G, Medaer R, Raus J, Stinissen P. Myelin reactive T cells after T cell vaccination in multiple sclerosis: cytokine profile and depletion by additional immunizations. J. Neuroimmunol 102, 79-84 (2000).
67. Zang YC, Hong J, Rivera VM, Killian J, Zhang JZ. Preferential recognition of TCR hypervariable regions by human antiidiotypic T cells induced by T cell vaccination. J. Immunol. 164, 4011-4017 (2000). (Pubitemid 30215054)
68. Vandenbark AA, Chou YK, Whitham R et al. Treatment of multiple sclerosis with T cell receptor peptides: results of a double-blind pilot trial. Nat. Med. 2, 1109-1115 (1996). (Pubitemid 26338630)
69. Minami Y, Weissman AM, Samelson LE, Klausner RD. Building a multichain receptor: synthesis, degradation, and assembly of the T cell antigen receptor. Proc. Natl Acad. Sci. USA 84, 2688-2692 (1987). (Pubitemid 17064716)
70. Broeren CP, Lucassen MA, van Stipdonk MJ et al. CDR1 T cell receptor β-chain peptide induces major histocompatibility complex class II-restricted T-T cell interactions. Proc. Natl Acad. Set. USA 91, 5997-6001 (1994). (Pubitemid 24188269)
71. Pamer E, Cresswell P. Mechanisms of MHC class I-restricted antigen processing. Ann. Rev. Immunol. 16, 323-358 (1998). (Pubitemid 28183368)
72. Zang YCQ, Hong J, Rivera VM, Killian J, Zhang JZ. Human anti-idiotypic T cells induced by TCR peptides corresponding to a common CDR3 sequence motif in myelin basic protein-reactive T cells. Int. Immunol. 15, 1073-1080 (2003). (Pubitemid 37063206)
73. Mor F, Reizis B, Cohen IR, Steinman L. IL-2 and TNF receptors as targets of regulatory T-T interactions: isolation and characterization of cytokine receptor-reactive T cell lines in the Lewis rat. J. Immunol. 157, 4855-4861 (1996). (Pubitemid 126449560)
74. + T cells. Immunity 2, 177-184 (1995).
75. Brod SA, Purvee M, Benjamin D, Hafler DA. T-T cell interactions are mediated by adhesion molecules. Eur. J. Immunol 20, 2259-2268 (1990). (Pubitemid 20368211)
76. regs in T cell vaccination: exploring the regulation of regulation. J. Clin. Invest. 114, 1227-1232 (2004). (Pubitemid 40385291)
77. Van der Aa A, Hellings N, Medaer K et al. T cell vaccination in multiple sclerosis patients with autologous CSF-derived activated T cells: results from a pilot study. Clin. Exp. Immunol. 131, 155-168 (2003). (Pubitemid 36098836)
78. Stinissen P, Zhang J, Vandevyver C, Hermans G, Raus J. γδ T cell responses to activated T cells in multiple sclerosis patients induced by T cell vaccination. J. Neuroimmunol 87, 94-104 (1998). (Pubitemid 28319849)
79. + T cells by different mechanisms. J. Neuroimmunol. 80, 47-64(1997). (Pubitemid 28015323)
80. Mimran A, Cohen IR. Regulatory T cells in autoimmune diseases: anti-ergotypic T cells. Int. Rev. Immunol. 24, 159-179 (2005). (Pubitemid 40990999)
81. + T cells restricted by the MHC class IB molecule, QA-l. Ann. Rev. Immunol. 18, 185-216 (2000). (Pubitemid 30365379)
82. + T cells in murine experimental allergic encephalomyelitis. Science 256, 1213-1215 (1992).
83. Koh DR, Fungleung WP, Ho A, Gray D, Achaorbea H, Mak TW. Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-/-mice. Science 256, 1210-1213(1992).
84. Jiang H, Chess L. An integrated view of suppressor T cell subsets in immuno-regulation. J. Clin. Invest. 114, 1198-208 (2004). (Pubitemid 40385287)
85. Hu D, Ikizawa K, Lu LR, Sanchirico ME, Shinohara ML, Cantor H. Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat. Immunol 5, 516-523 (2004). (Pubitemid 38660464)
86. Jiang H, Kashleva H, Xu LX et al. T cell vaccination induces T cell receptor Vβ-specific Qa-1-restricted regulatory CD8(+) T cells. Proc. Natl Acad. Sci. USA 95, 4533-4537 (1998). (Pubitemid 28207947)
87. Panoutsakopoulou V, Huster KM, McCarty N et al. Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes. J. Clin. Invest. 113, 1218-1224 (2004). (Pubitemid 38544107)
88. Jiang H, Wu YL, Liang BT et al. An affinity/avidity model of peripheral T cell regulation. J. Clin. Invest. 115, 302-312(2005). (Pubitemid 40385472)
89. Li JF, Goldstein I, Glickman-Nir E, Jiang H, Chess L. Induction of TCR V P-specific CD8(+) CTLs by TCR V β-derived peptides bound to HLA-E. J. Immunol. 167, 3800-3808 (2001). (Pubitemid 32910825)
90. Garcia P, Llano M, De Heredia AB et al. Human T cell receptor-mediated recognition of HLA-E. Eur. J. Immunol. 32, 936-944 (2002). (Pubitemid 34428808)
91. Hashim GA, Offner H, Wang RY et al. Spontaneous development of protective anti-T cell receptor autoimmunity targeted against a natural EAE-regulatory idiotope located within the 39-59 region of the TCR-V β 8.2 chain. J. Immunol. 149, 2803-2809 (1992).
92. Hong J, Zang YC, Tejada-Simon MV et al. Reactivity and regulatory properties of human anti-idiotypic antibodies induced by T cell vaccination. J. Immunol. 165, 6858-6864 (2000). (Pubitemid 32001154)
93. Shevach EM. Regulatory T cells in autoimmmunity. Ann. Rev. Immunol. 18, 423-449 (2000). (Pubitemid 30365387)
94. Chatenoud L. Do NKT cells control autoimmunity? J. Clin. Invest. 110, 747-748 (2002).
95. + regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 199, 971-979(2004). (Pubitemid 38481088)
96. Venken K, Hellings N, Hensen K et al. Secondary progressive in contrast to relapsing-remitting multiple sclerosis patients show a normal CD4(+)CD25(+) regulatory T cell function and FOXP3 expression. J. Neurosci. Res. 83, 1432-1446 (2006). (Pubitemid 43844989)
97. Huan J, Culbertson N, Spencer L et al. Decreased FOXP3 levels in multiple sclerosis patients. J. Neurosci. Res. 81, 45-52 (2005). (Pubitemid 41139109)
98. + T cells. Curr. Drug Targets Inflamm. Allergy 4, 217-229 (2005). (Pubitemid 40873104)
99. Offner H, Vandenbark AA Congruent effects of estrogen and T cell receptor peptide therapy on regulatory T cells in EAE and MS. Int. Rev. Immunol 24, 447-177 (2005).
100. Markovic-Plese S, Fukaura H, Zhang J et al. T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans. J. Immunol 155, 982-992 (1995).
101. Pelfrey CM, Tranquill LR, Vogt AB, McFarland HF. T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls. Mult. Scler. 1, 270-278 (1996). (Pubitemid 126701319)
102. Kerlero De Rosbo N, Milo R, Lees MB, Burger D, Bernard CC, Ben Nun A. Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominandy to myelin oligodendrocyte glycoprotein. J. Clin. Invest. 92, 2602-2608 (1993). (Pubitemid 24006523)
103. Diaz-Vdloslada P, Shih A, Shao L, Genain CP, Häuser SL. Autoreactivity to myelin antigens: myelin/oligodendrocyte glycoprotein is a prevalent autoantigen. J. Neuroimmunol 99, 36-43 (1999). (Pubitemid 29488567)
104. Hellings N, Gelin G, Medaer R et al. Longitudinal study of anrimyelin T cell reactivity in relapsing-remitting multiple sclerosis: association with clinical and MRI activity. J. Neuroimmunol 126, 143-160 (2002). (Pubitemid 34521740)
105. Stinissen P, Medaer R, Raus, J. Preliminary data of an extended open label phase I study of T cell vaccination in multiple sclerosis. J. Neuroimmunol 90, 99 (1998).
106. Vandenbark AA, Hashim G, Offner H. Immunization with a synthetic T cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature 341, 541-544 (1989). (Pubitemid 19252528)
107. Howell MD, Winters ST, Olee T, Powell HC, Carlo DJ, Brostoff SW. Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. Science 246, 668-670 (1989). (Pubitemid 19283360)
108. Kotzin BL, Karuturi S, Chou YK et al. Preferential T cell receptor β-chain variable gene use in myelin basic protein-reactive T cell clones from patients with multiple sclerosis. Proc. Natl Acad. Sci. USA 88, 9161-9165 (1991). (Pubitemid 21915589)
109. Bourdette DN, Whitham RH, Chou YK et al. Immunity to TCR peptides in multiple sclerosis. I. Successful immunization of patients with synthetic V β 5.2 and V β 6.1 CDR2 peptides. J. Immunol. 152, 2510-2519 (1994). (Pubitemid 24097944)
110. Chou YK, Morrison WJ, Weinberg AD et al. Immunity to TCR peptides in multiple sclerosis. II. T cell recognition of V β 5.2 and V β 6.1 CDR2 peptides. J. Immunol 152, 2520-2529 (1994). (Pubitemid 24097945)
111. Hafler DA, Cohen I, Benjamin DS, Weiner HL. T cell vaccination in multiple sclerosis: a preliminary report. Clin. Immunol. Immunopathol 62, 307-313 (1992).
112. Hellings N, Raus J, Stinissen P. T cell vaccination in multiple sclerosis: update on clinical application and mode of action. Autoimmun. Rev. 3, 267-275 (2004). (Pubitemid 38887622)