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Advances in the Immunopathogenesis of Multiple Sclerosis pp 11–19Cite as

The naïve and memory MBP-reactive CD4+ T cell repertoire: implications for the autoimmune concept in multiple sclerosis

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Abstract

T cells reacting to self-antigens may be involved in the pathogenesis of human autoimmune diseases, such as multiple sclerosis (MS). The pathogenesis of MS is currently ascribed, at least in part, to a T cell-mediated process targeting myelin components [1].Among myelin proteins, myelin basic protein (MBP) is a major candidate autoantigen in MS. The evidence supporting this claim has been examined in several excellent reviews [1–4], and includes the following well established observations: (1) degradation products of MBP are present in macrophages surrounding MS lesions; (2) MBP content in plaques is reduced; (3) the protein is relatively abundant (~30%) in central nervous system (CNS) myelin and (4) the immunodominant T cell epitope clusters of MBP [N-terminal (1–11, 1–19), central (87–106, 83–99, 87–99, 84–102), central (111–129, 115–125), C-terminal (143–168, 131–159)] are predominantly recognized in the context of MS-associated HLA-DR molecules [5–10].

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References

  1. Martin R, McFarland HF, McFarlin DE (1992) Immunological aspects of demyelinating diseases. Annu Rev Immunol 10: 153–187

    Article  PubMed  CAS  Google Scholar 

  2. Hafler DA, Weiner HL (1995) Immunologic mechanisms and therapy in multiple sclerosis. Immunol Rev 144: 75–107

    Article  PubMed  CAS  Google Scholar 

  3. Steinman L (1996) Multiple sclerosis: a coordinated immunological attack against myelin in the central nervous system. Cell 85: 299–302

    Article  PubMed  CAS  Google Scholar 

  4. Martin R, McFarland HF (1997) Immunology of multiple sclerosis and experimental allergic encephalomyelitis. In: Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. Chapman & Hall, London, pp 221–242

    Google Scholar 

  5. Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA (1990) T cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346: 183–187

    Article  PubMed  CAS  Google Scholar 

  6. Chou YK, Henderikx P, Vainiene M, Whitham RH, Bourdette DN, Chou CH, Hashim GA, Offner H, Vandenbark AA (1991) Specificity of human T cell clones reactive to immunodominant epitopes of myelin basic protein. J Neurosci Res 28: 280–290

    Article  PubMed  CAS  Google Scholar 

  7. Martin R, Jaraquemada D, Flerlage M, Richert JR, Whitaker JN, Long EO, McFarlin DE, McFarland HF, Richert J, Whitaker J (1990) Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. J Immunól 145: 540–548

    PubMed  CAS  Google Scholar 

  8. Zhang J, Medaer R, Hashim GA, Chin Y, van den Berg-Loonen E, Raus JC (1992) Myelin basic protein-specific T lymphocytes in multiple sclerosis and controls: precursor frequency, fine specificity, and cytotoxicity. Ann Neurol 32: 330–338

    Google Scholar 

  9. Valli A, Sette A, Kappos L, Oseroff C, Sidney J, Miescher G, Hochberger M, Albert ED, Adorini L (1993) Binding of myelin basic protein peptides to human histocompatibility leukocyte antigen class II molecules and their recognition by T cells from multiple sclerosis patients. J Clin Invest 91: 616–628

    Article  PubMed  CAS  Google Scholar 

  10. Muraro PA, Vergelli M, Kalbus M, Banks D, Nagle JW, Tranquill LR, Nepom GT, Biddison WE, McFarland HF, Martin R (1997) Immunodominance of a low-affinity MHC binding myelin basic protein epitope (residues 111–129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire. J Clin Invest 100: 339–349

    Article  PubMed  CAS  Google Scholar 

  11. Pette M, Fujita K, Kitze B, Whitaker JN, Albert E, Kappos L, Wekerle H (1990) Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology 40: 1770–1776

    PubMed  CAS  Google Scholar 

  12. Lovett-Racke AE, Trotter JL, Lauber J, Perrin PJ, June CH, Racke MK (1998) Decreased dependence of myelin basic protein-reactive T cells on CD28mediated costimulation in multiple sclerosis patients. J Clin Invest 101: 725–730

    Article  PubMed  CAS  Google Scholar 

  13. Scholz C, Patton KT, Anderson DE, Freeman GJ, Hafler DA (1998) Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. J Immunol 160: 1523–1538

    Google Scholar 

  14. Wucherpfennig KW, Strominger JL (1995) Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80: 695–705

    Article  PubMed  CAS  Google Scholar 

  15. Hemmer B, Fleckenstein BT, Vergelli M, Jung G, McFarland HF, Martin R, Wiesmuller K-H (1997) Identification of high potency microbial and self ligands for a human autoreactive class II-restricted T cell clone. J Exp Med 185: 1651–1659

    Article  PubMed  CAS  Google Scholar 

  16. Vitetta ES, Berton MT, Burger C, Kepron M, Lee WT, Yin XM (1991) Memory B and T cells. Annu Rev Immunol 9: 193–217

    Article  PubMed  CAS  Google Scholar 

  17. Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12: 991–1045

    Article  PubMed  CAS  Google Scholar 

  18. Swain SL, Croft M, Dubey C, Haynes L, Rogers P, Zhang X, Bradley LM (1996) From naive to memory T cells. Immunol Rev 150: 143–167

    Article  PubMed  CAS  Google Scholar 

  19. Schweighoffer T, Luce GE, Tanaka Y, Shaw S (1994) Differential expression of integrins alpha 6 and alpha 4 determines pathways in human peripheral CD4+ T cell differentiation. Cell Adhes Commun 2: 403–415

    Article  PubMed  CAS  Google Scholar 

  20. Horgan KJ, Luce GE, Tanaka Y, Schweighoffer T, Shimizu Y, Sharrow SO, Shaw S (1992) Differential expression of VLA-alpha 4 and VLA-beta 1 discriminates multiple subsets of CD4+CD45R0+ “memory” T cells. J Immunol 149: 4082–4087

    PubMed  CAS  Google Scholar 

  21. Byrne JA, Butler JL, Cooper MD (1988) Differential activation requirements for virgin and memory T cells. J Immunol 141: 3249–3257

    PubMed  CAS  Google Scholar 

  22. Croft M, Swain SL (1995) Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines. J Immunol 154: 4269–4282

    PubMed  CAS  Google Scholar 

  23. Dubey C, Croft M, Swain SL (1995) Costimulatory requirements of naive CD4+ T cells. ICAM-1 or B7–1 can costimulate naive CD4 T cell activation but both are required for optimum response. J Immunol 155: 45–57

    PubMed  CAS  Google Scholar 

  24. Lee WT, Vitetta ES (1991) The differential expression of homing and adhesion molecules on virgin and memory T cells in the mouse. Cell Immunol 132: 215–222

    Article  PubMed  CAS  Google Scholar 

  25. Bradley LM, Watson SR, Swain SL (1994) Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin. J Exp Med 180: 2401–2406.

    Article  PubMed  CAS  Google Scholar 

  26. Bell EB, Sparshott SM (1990) Interconversion of CD45R subsets of CD4 T cells in vivo. Nature 348: 163–166

    Article  PubMed  CAS  Google Scholar 

  27. Bunce C, Bell EB (1997) CD45RC isoforms define two types of CD4 memory T cells, one of which depends on persisting antigen. J Exp Med 185: 767–776

    Article  PubMed  CAS  Google Scholar 

  28. Hamann D, Baars PA, Rep MHG, Hooibrink B, Kerkhof-Garde SR, Klein MR, Lier RAW (1997) Phenotypic and functional separation of memory and effector human CD8(+) T cells. J Exp Med 186: 1407–1418

    Article  PubMed  CAS  Google Scholar 

  29. Smith SH, Brown MH, Rowe D, Callard RE, Beverley PCL (1986) Functional subsets of human help-inducer cells defined by a new monoclonal antibody, UCHL1. Immunology 58: 63

    PubMed  CAS  Google Scholar 

  30. Akbar AN, Terry L, Timms A, Beverley PCL, Janossy G (1988) Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol 140: 2171–2178

    PubMed  CAS  Google Scholar 

  31. Allegretta M, Nicklas JA, Sriram S, Albertini RJ (1990) T cells responsive to myelin basic protein in patients with multiple sclerosis. Science 247: 718721

    Google Scholar 

  32. Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA (1994) Increased frequency of interleukin 2-responsive T 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

    Article  PubMed  CAS  Google Scholar 

  33. Michie CA, McLean AR, Alcock C, Beverley PCL (1992) Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature 360: 264–265

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. P. A. Muraro
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  2. B. Bielekova
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Editors and Affiliations

  1. Department of Oncology and Neuroscience, Medical School, University G. D’Annunzio, Chieti, Italy

    D. Gambi , P. A. Muraro  & A. Lugaresi ,  & 

  2. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA

    P. A. Muraro

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© 1999 Springer-Verlag Italia, Milan

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Muraro, P.A., Bielekova, B. (1999). The naïve and memory MBP-reactive CD4+ T cell repertoire: implications for the autoimmune concept in multiple sclerosis. In: Gambi, D., Muraro, P.A., Lugaresi, A., Ecari, U. (eds) Advances in the Immunopathogenesis of Multiple Sclerosis. Springer, Milano. https://doi.org/10.1007/978-88-470-2269-0_3

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  • DOI: https://doi.org/10.1007/978-88-470-2269-0_3

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-0067-4

  • Online ISBN: 978-88-470-2269-0

  • eBook Packages: Springer Book Archive

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