Molecular approach to find target(s) for oligoclonal bands in multiple sclerosis
a Department of
Pathology and Laboratory Medicine, b Department of Biochemistry, c Department of Neurology, College of Medicine,
University of Florida, USA Department of
Veteran's Affairs Medical Center, Gainesville, Florida 32610, USA
Correspondence to: Dr Kenneth H Rand, University of Florida, Department of Pathology, Box 100275, JHMHC, Gainesville, FL 32610-0275, USA. Tel: 001 352 392 5621;Fax: 001 352 392 4693.
Received 9
September 1997 and in revised form 9 December 1997;
Accepted 9 December 1997
OBJECTIVES
Oligoclonal
bands are a characteristic finding in the CSF of patients with multiple
sclerosis, yet their target antigen(s) remain unknown. The objective
was to determine whether a filamentous phage peptide library could be
employed to allow the oligoclonal bands to select their own target epitopes.
METHODSCSF IgG
antibody from 14 patients with multiple sclerosis and 14 controls was
used to select individual phage clones from a bacteriophage library
containing
4 × 107 different hexamers expressed on its
surface pIII protein. The amino acid sequence selected was deduced by
sequencing the DNA of the genetically engineered insert.
RESULTSIn general,
after three rounds of selection, CSF from both patients with multiple
sclerosis and controls selected one to two consistent peptide motifs.
Five out of 14 patients with multiple sclerosis, and one control,
selected the amino acid sequence motif, RRPFF. Given 20 possible amino
acids per position, the likelihood of five patients selecting the same
linear five amino acid sequence is at most 1.6 × 10-13,
corrected for the number of clones sequenced. A GenBank computer search
showed that this sequence is found in the Epstein-Barr Virus nuclear
antigen (EBNA-1), and a heat shock protein 
B crystallin. Human serum
antibodies to a synthetic peptide containing RRPFF were virtually
exclusively found in patients with prior infection by Epstein-Barr
virus. Other studies have suggested a relation between Epstein-Barr
virus infection and multiple sclerosis, including nearly 100%
Epstein-Barr virus seropositivity among patients with multiple
sclerosis and increased concentrations of
antibody to EBNA in CSF of patients with multiple sclerosis. By antigen
specific immunoblotting, antibodies to the RRPFF motif in the CSF were shown to correspond to a subset of oligoclonal bands in the CSF from
the same patient.
CONCLUSIONThis study
shows that phage epitope display libraries may be used to select amino
acid motifs which are potentially relevant to the pathogenesis of
multiple sclerosis.
© 1998 by Journal of Neurology, Neurosurgery, and Psychiatry
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