| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Medicine and Microbiology and Immunology and
Pathology, College of Medicine, State University of New York, Syracuse, NY 13210;
Wistar Institute and the University of Pennsylvania, Philadelphia, PA 19104; and
§
Department of Biomedical Engineering, Boston University, Boston, MA 02215
Multiple sclerosis is mediated by an autoimmune process causing
selective destruction of oligodendrocytes. Transaldolase, which is
expressed in the brain selectively in oligodendrocytes, is a target of
high affinity autoantibodies in serum and cerebrospinal fluid of
multiple sclerosis patients. A three-dimensional model of human
transaldolase was developed based on the crystal structure of the
enzyme from Escherichia coli. To identify immunodominant
epitopes, 33 peptides overlapping human transaldolase by 5 amino acids
were synthesized. Ab 12484, raised against enzymatically active human
transaldolase, recognized antigenic determinants corresponding to
linear epitopes (residues 27–31 and 265–290) and 
helices
(residues 75–98 and 302–329). Four immunodominant peptides harboring
charged amino acid residues with topographically exposed side chains
were identified by sera from 13 multiple sclerosis patients with
predetermined autoreactivity to transaldolase. Autoantibodies binding
to the most prominent human transaldolase epitope, between residues 271
and 285, showed cross-reactivity with Epstein-Barr and herpes simplex
virus type 1 capsid-derived peptides. Molecular mimicry between
immunodominant autoepitopes and viral Ags may be a decisive factor in
directing autoimmunity to transaldolase in multiple sclerosis
patients.
This article has been cited by other articles:
|
|
 |
|
  S. Schneider, T. Sandalova, G. Schneider, G. A. Sprenger, and A. K. Samland Replacement of a Phenylalanine by a Tyrosine in the Active Site Confers Fructose-6-phosphate Aldolase Activity to the Transaldolase of Escherichia coli and Human Origin J. Biol. Chem., October 31, 2008; 283(44): 30064 - 30072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Mayo, J. Arribas, P. Villoslada, R. Alvarez DoForno, S. Rodriguez-Vilarino, X. Montalban, M. R. de Sagarra, and J. G. Castano The proteasome is a major autoantigen in multiple sclerosis Brain, December 1, 2002; 125(12): 2658 - 2667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Embry, R. A. Marrie, C. Wolfson, M. C. J. M. Sturkenboom, O. Gout, O. Heinzlef, E. Roullet, and L. Abenhaim Multiple sclerosis and antecedent infections: A case-control study Neurology, January 23, 2001; 56(2): 282 - 283. [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Whitbeck, S. A. Connolly, S. H. Willis, W. Hou, C. Krummenacher, M. Ponce de Leon, H. Lou, I. Baribaud, R. J. Eisenberg, and G. H. Cohen Localization of the gD-Binding Region of the Human Herpes Simplex Virus Receptor, HveA J. Virol., January 1, 2001; 75(1): 171 - 180. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
