| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology,
Department of Internal Medicine, and
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany
Genetic deficiency or instability of myelin protein zero (P0) results in hereditary motor sensory neuropathy. In view of recent advances in gene therapy, substitution of the molecular defect may become realistic in the near future. Here we investigate the impact of genetic deficiency of P0 on selection of the autoreactive T cell repertoire in the corresponding mouse model. We show that P0 mRNA transcripts are expressed in thymic stroma, similar to other myelin proteins and that expression of intact P0 protein can be detected by Western blot. Using a library of overlapping 20mer peptides spanning the entire length of P0 and applying the ELISPOT technique, we detected a strong immune response toward P0 extracellular domain peptide aa 41–60 in P0-/- knockout mice, but not in heterozygous P0+/- or wild-type (wt) mice. In addition, one cryptic epitope and two subdominant epitopes of P0 were identified. Using P0-/- into wt bone marrow (BM) chimeras we found that P0 expression in the host suffices for full tolerance induction, which is in line with its presence in thymic stroma. However, repopulation of P0-/- mice with wt BM led to partial induction of tolerance, suggesting that BM derived cells can also express this protein. Our findings may have implications for secondary autoimmunity developing after gene therapy in hereditary neuropathies and other diseases with genetically determined protein deficiency, because the repaired protein will then represent a foreign, nontolerized Ag.
This article has been cited by other articles:
|
|
 |
|
  C. Louvet, B. G. Kabre, D. W. Davini, N. Martinier, M. A. Su, J. J. DeVoss, W. L. Rosenthal, M. S. Anderson, H. Bour-Jordan, and J. A. Bluestone A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy J. Exp. Med., March 16, 2009; 206(3): 507 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Kim, C.-G. Jung, M. A. Jensen, D. Dukala, and B. Soliven Targeting of Myelin Protein Zero in a Spontaneous Autoimmune Polyneuropathy J. Immunol., December 15, 2008; 181(12): 8753 - 8760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Perchellet, T. Brabb, and J. M. Goverman Crosspresentation by nonhematopoietic and direct presentation by hematopoietic cells induce central tolerance to myelin basic protein PNAS, September 16, 2008; 105(37): 14040 - 14045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hayer, M. Tohidast-Akrad, S. Haralambous, B. Jahn-Schmid, K. Skriner, S. Trembleau, H. Dumortier, S. Pinol-Roma, K. Redlich, G. Schett, et al. Aberrant Expression of the Autoantigen Heterogeneous Nuclear Ribonucleoprotein-A2 (RA33) and Spontaneous Formation of Rheumatoid Arthritis-Associated Anti-RA33 Autoantibodies in TNF-{alpha} Transgenic Mice J. Immunol., December 15, 2005; 175(12): 8327 - 8336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Plaisier, B. Mougenot, M. C. Verpont, C. Jouanneau, J. J. Archelos, R. Martini, D. Kerjaschki, and P. Ronco Glomerular Permeability Is Altered by Loss of P0, a Myelin Protein Expressed in Glomerular Epithelial Cells J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3350 - 3356. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
