More MS news articles for August 2002

Truncation of the neuritogenic peptide bP2(60-70) results in the generation of altered peptide ligands with the potential to interfere with T cell activation

http://www.elsevier.com/gej-ng/10/27/37/131/27/38/abstract.html

Journal of Neuroimmunology, Vol. 129 (1-2) (2002) pp. 97-105
Martin Offenhäusser a 1,2 , Alexandra S. Herr a 2, Jörg Hartkamp b, Marca Wauben c, Tim Magnus a 1, Oliver Grauer a, Silvia Seubert a 1, Andreas Weishaupt a, Klaus V. Toyka a, Ralf Gold a and Jakob Troppmair * b
a Clinical Research Group for Multiple Sclerosis and Neuroimmunology, Department of Neurology, Julius-Maximilians-University, Würzburg, Germany
b Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Julius-Maximilians-University, Würzburg, Germany, Verbacher Str. 5, 97078 Würzburg, Germany
c Faculty of Veterinary Medicine, Institute of Infectious Disease and Immunology, Utrecht University, Utrecht, Netherlands

Due to the central role of T cells in the pathogenesis of inflammatory diseases of the peripheral nervous system like the Guillain-Barré syndrome, specific immunotherapies aim at modifying T cell responses.

Use of truncated mutants of the neuritogenic peptide of myelin basic protein (MBP) has been shown to anergize autoreactive T cells and to reverse experimental autoimmune encephalitis (EAE).

To establish a rationale basis for the use of altered peptide ligands (APLs) in the treatment of autoimmune diseases we designed a set of N- and C-terminally truncated mutants of the minimal experimental autoimmune neuritis (EAN) inducing bovine P2 (bP2) (60-70) peptide and compared them for the ability to induce immune responses and T cell receptor (TCR) cell signaling.

Truncated peptides bound to MHC class II molecules and induced TCR internalization and expression of interferon  (IFN-) and tumor necrosis factor  (TNF-) with decreasing potency.

None of the shortened mutants elicited a proliferative response in P2-specific T cells.

Stimulation of these antigen-specific T cells with peptide bP2(62-69) using antigen presenting cells (APCs) prepulsed with bP2(60-70) resulted in a significant decrease of the proliferative response.

In agreement with the observed effects on T cell activation, analysis of TCR signaling demonstrated a lack of CD3 phosphorylation and MAPK activation.

Moreover, repeated injection of bP2(62-69) significantly slowed progression of adoptive transfer EAN (AT-EAN).

Taken together, these findings strongly suggest that peptide bP2(62-69) can favorably modulate the antigen-induced response of neuritogenic T cells.

© 2002 Elsevier Science B.V.