IgG oligoclonal bands (OCBs) are present in the cerebrospinal fluid (CSF) of more than 95% of patients with
multiple sclerosis (MS), and are considered to be the immunological hallmark of disease. However, the target specificities of the
IgG in MS OCBs have remained undiscovered. Nevertheless, evidence that OCBs are associated with increased levels of disease activity and disability support their probable pathological role in MS. We investigated the
antigen specificity of individual MS CSF
IgG from 20 OCB-positive patients and identified 40 unique
peptides by panning phage-displayed
random peptide libraries. Utilizing our unique techniques of phage-mediated real-time Immuno-PCR and phage-probed isoelectric focusing immunoblots, we demonstrated that these
peptides were targeted by intrathecal
oligoclonal IgG antibodies of
IgG1 and
IgG3 subclasses. In addition, we showed that these
peptides represent
epitopes sharing sequence homologies with
proteins of viral origin, and
proteins involved in cell stress, apoptosis, and inflammatory processes. Although homologous
peptides were found within individual patients, no shared
peptide sequences were found among any of the 42 MS and 13 inflammatory CSF control specimens. The distinct sets of
oligoclonal IgG-reactive
peptides identified by individual MS CSF suggest that the elevated intrathecal
antibodies may target patient-specific
antigens.