| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Neuroimmunology Unit, Center of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden; and
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden
The underlying mechanisms behind the preferential expression of select TCRBV products in certain autoimmune illnesses, such as multiple sclerosis and some models of experimental autoimmune encephalomyelitis (EAE), have principally remained enigmatic. In this study, we examined the mutual role of nonself- vs self-origin of antigenic myelin basic protein (MBP) peptides and given MHC haplotypes in relation to the relative frequency of activated TCRBV8S2+ T lymphocytes in the Lewis (LEW) rat EAE model. Inbred MHC (RT1) congenic LEW rats (LEW (RT1l), LEW.1AV1 (RT1av1), and LEW.1W (RT1u)) were immunized with the 63 to 88 peptide of the guinea pig MBP (MBPGP63-88). Additionally, LEW rats were immunized with the corresponding autologous rat sequence (MBPRAT63-88). Although EAE ensued in all MBP peptide/LEW rat strain combinations, only LEW rats immunized with the heterologous MBPGP63-88 peptide elicited T cell responses encompassing a bias toward TCRBV8S2 expression, as determined by flow cytometric analyses. Reduction of TCRBV8S2+ T cells led to mitigation of disease severity in LEW rats immunized with MBPGP63-88, but not with MBPRAT63-88, indicating that critical encephalitogenic characteristics are associated with this T cell subset. We conclude that the preferential recruitment of TCRBV8S2+ T cells in the LEW rat EAE model is due to selective, high-avidity recognition of the nonself-MBPGP63-88 in the context of the RT1.Bl molecule. This inference lends support to the notion that the highly restricted TCR repertoire of the self-MBP-reactive T cells in certain genetically predisposed multiple sclerosis patients may have its source in a multistep molecular mimicry event.
This article has been cited by other articles:
|
|
 |
|
  N. Fissolo, S. Haag, K. L. de Graaf, O. Drews, S. Stevanovic, H. G. Rammensee, and R. Weissert Naturally Presented Peptides on Major Histocompatibility Complex I and II Molecules Eluted from Central Nervous System of Multiple Sclerosis Patients Mol. Cell. Proteomics, September 1, 2009; 8(9): 2090 - 2101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zhou, R. Srivastava, S. Nessler, V. Grummel, N. Sommer, W. Bruck, H.-P. Hartung, C. Stadelmann, and B. Hemmer Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis PNAS, December 12, 2006; 103(50): 19057 - 19062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Weissert, K. L. de Graaf, M. K. Storch, S. Barth, C. Linington, H. Lassmann, and T. Olsson MHC Class II-Regulated Central Nervous System Autoaggression and T Cell Responses in Peripheral Lymphoid Tissues Are Dissociated in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis J. Immunol., June 15, 2001; 166(12): 7588 - 7599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hammarberg, O. Lidman, C. Lundberg, S. Y. Eltayeb, A. W. Gielen, S. Muhallab, A. Svenningsson, H. Linda, P. H. van der Meide, S. Cullheim, et al. Neuroprotection by Encephalomyelitis: Rescue of Mechanically Injured Neurons and Neurotrophin Production by CNS-Infiltrating T and Natural Killer Cells J. Neurosci., July 15, 2000; 20(14): 5283 - 5291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lobell, R. Weissert, S. Eltayeb, C. Svanholm, T. Olsson, and H. Wigzell Presence of CpG DNA and the Local Cytokine Milieu Determine the Efficacy of Suppressive DNA Vaccination in Experimental Autoimmune Encephalomyelitis J. Immunol., November 1, 1999; 163(9): 4754 - 4762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Smeltz, M. H. M. Wauben, N. A. Wolf, and R. H. Swanborg Critical Requirement for Aspartic Acid at Position 82 of Myelin Basic Protein 73-86 for Recruitment of V{beta}8.2+ T Cells and Encephalitogenicity in the Lewis Rat J. Immunol., January 15, 1999; 162(2): 829 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weissert, A. Lobell, K. L. de Graaf, S. Y. Eltayeb, R. Andersson, T. Olsson, and H. Wigzell Protective DNA vaccination against organ-specific autoimmunity is highly specific and discriminates between single amino acid substitutions in the peptide autoantigen PNAS, February 15, 2000; 97(4): 1689 - 1694. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
