Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis
Sabine Cepok, … , Norbert Sommer, Bernhard Hemmer
Sabine Cepok, … , Norbert Sommer, Bernhard Hemmer
Published May 2, 2005
Citation Information: J Clin Invest. 2005;115(5):1352-1360. https://doi.org/10.1172/JCI23661.
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Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis

Abstract

MS is a chronic inflammatory and demyelinating disease of the CNS with as yet unknown etiology. A hallmark of this disease is the occurrence of oligoclonal IgG antibodies in the cerebrospinal fluid (CSF). To assess the specificity of these antibodies, we screened protein expression arrays containing 37,000 tagged proteins. The 2 most frequent MS-specific reactivities were further mapped to identify the underlying high-affinity epitopes. In both cases, we identified peptide sequences derived from EBV proteins expressed in latently infected cells. Immunoreactivities to these EBV proteins, BRRF2 and EBNA-1, were significantly higher in the serum and CSF of MS patients than in those of control donors. Oligoclonal CSF IgG from MS patients specifically bound both EBV proteins. Also, CD8+ T cell responses to latent EBV proteins were higher in MS patients than in controls. In summary, these findings demonstrate an increased immune response to EBV in MS patients, which suggests that the virus plays an important role in the pathogenesis of disease.

Authors

Sabine Cepok, Dun Zhou, Rajneesh Srivastava, Stefan Nessler, Susanne Stei, Konrad Büssow, Norbert Sommer, Bernhard Hemmer

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Frequency and phenotype of EBV-specific T cells in MS patients and healt...
Frequency and phenotype of EBV-specific T cells in MS patients and healthy donors. (A) Strategy for detection of EBV-specific T cells in PBMC samples by intracellular IFN-γ staining and flow cytometry. PBMCs and autologous EBV-transformed B cell lines were either cultured separately (nonspecific activation, left graph) or in short-term coculture (EBV-specific activation, right graph) before staining. Shown are analyses of CD8+ T cells in the CD28+ and CD28– compartments of an MS patient. One percent of CD8+CD28+ T cells were EBV-specific in this patient. (B) Frequency of EBV-specific CD4+ and CD8+ T cells in 11 MS patients and 14 healthy donors (HD). No significant differences were observed in the CD4+ T cell compartments, whereas a higher frequency of EBV-specific CD8+ T cells was observed in MS patients. Further characterization revealed a significantly higher frequency of EBV-specific CD8+CD28+ in MS patients compared with healthy controls. Student’s t test was applied.