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Department of Neurology

Houston, Texas

BCM neurologists see patients through the Baylor Clinic and some of the world's leading specialty clinics.
Department of Neurology
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T Cell-Mediated Autoimmune Mechanism in MS

Principal Investigators

Jingwu Zhang, M.D., Ph.D.
Jian Hong, M.D., Ph.D.
Sheri Skinner, Ph.D
Wei Sun, M.D., Ph.D.

Summary

The research interests of our laboratory are (1) autoreactive T cell responses to myelin antigens, including myelin basic protein (MBP) and proteolipid protein (PLP), and their role in the pathogenesis of multiple sclerosis (MS); (2) the structural and functional properties of myelin autoreactive T cells and their relevance to the disease process; (3) the nature and antigen specificity of autoreactive T cells in the brain compartment of patients with MS; and (4) clonotypic regulation of autoreactive T cells and their therapeutic implication in the treatment of MS.

Autoreactive T cells recognizing myelin antigens are found to undergo in vivo activation and clonal expansion in patients with MS. They accumulate in the cerebrospinal fluid and perpetuate in the brain lesions of MS. The presence of these myelin autoreactive T cells in the CNS suggests their potential participation in the pathogenesis of MS and has prompted clinical trials investigating the effects of their depletion.

Characterization of MBP-Specific T Cell Clones

Characterization of MBP-specific T Cell Clones.

Expression of the LGRAGLITY motif in 44 MBP(83-99) specific T cells derived from four MS patients.

Expression of the LGRAGLITY motif in 44 MBP83-99 specific T cells derived from four MS patients.

Selected References

  1. Zhang, J., Markovic, S., Lacet, B., Raus, J., Weiner, H. and Hafler, D. (1994) Increased frequency of IL-2 responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with MS. Journal of Experimental Medicine 179: 973.
  2. Wucherpfenning, K., Zhang, J., Witek, C., Matsui, M., Modabber, Y., Ota, K. and Hafler, D. (1994) Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. Journal of Immunology 152:5581.
  3. Stinissen, P., Vandevyver, C., Smeyers, E., Vandegaer, L., Nies, J., Tuyls, L. Meadaer, R. Raus, J. and Zhang J. (1995) Increased frequency of gamma delta T cells in multiple sclerosis: functional properties and T cell receptor V gene usage. Journal of Immunology 154:4883.
  4. Vandevyver, C., Mertens, N., Van den Elsen, P., Raus, J. and Zhang, J. (1998) Limited heterogeneity in TCR V alpha gene arrangements of DR2-restricted T cells recognizing an immunodominant peptide of MBP in multiple sclerosis. International Immunology 10:991.
  5. Zang, Y., Kozovska, M., Aebischer, I., Rivera, V., Luo, W., Crowe, P., Boehme, S. and Zhang, J. (1998) Limited heterogeneity in TCR V alpha gene rearrangements of DR2-restricted T cells recognizing an immunodominant peptide of MBP in multiple sclerosis. International Immunology 10:991.
  6. Hong, J., Zang, Y., Li, S., Killian, J.M., Rivera, V.M. and Zhang, J. (1999) A common TCR sequence motif shared by myelin basic protein-reactive T cells in patients with multiple sclerosis. J Immunol. 163:3530.
  7. Tejada-Simon, M., Yang, D., Zang, Y. and Zhang, J. (2000) T cell reactivity to myelin antigens and their structural and functional properties at different clinical stages of multiple sclerosis. Int Immunol. 12:1641.
  8. Tejada-Simon, M., Hong, J., Rivera, V., and Zhang, J. (2002) Aberrant antoantibody reactivity to extracellular domain of myelin oligodendrocyte glycoprotein in multiple screrosis.
  9. Kisco, K., Zang, Y., Yang, D., Hong, J., Rivera, V., and Zhang, J. (1999) Increased frecuency of myelin basic protein-reactive T cells in patients with spinal cord injury. J Neuroimmunol. 98:201.
  10. Tejada-Simon, M., Hong, J., Rivera, V., and Zhang, J.(2001) Reactivity pattern and cytokine profile of T cells primed by myelin peptides in multiple sclerosis and healthy individuals. Eur J Immunol. 3:907.
  11. Godkin, A., Smith, K., Willis, A., Tejada-Simon, M., Zhang, J., Elliott, T., and Hill, A.(2001) Naturally processed HLA class II peptides reveal highly conserved immunogenic flanking region sequence preferences that reflect antigen processing rather than peptide-MHC interactions. J Immunol. 166, 6720-6727.
  12. Tejada-Simon, M., Hong, J., Rivera, V., and Zhang, J. (2002) Skewed autoantibody reactivity to the extracellular domain of myelin oligodendrocyte glycoprotein in multiple sclerosis. Immunol. 107, 403-410.
  13. Tejada-Simon, M., Zang, Y., Hong, J., Rivera, V., and Zhang J., (2003) Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann Neurol. 53, 189-197.
  14. Zang, Y., Sutang, Li., Hong, J., Rivera, V., and Zhan, J. (2003) CD8 cytotoxic T cell response to peptides of myelin basic protein in multiple sclerosis and healthy controls. J. Immunol. (In revision).