Brain, Vol. 122, No. 11, 2089-2100,
November 1999
© 1999 Oxford University Press
Invited review |
Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein
1 Department of Neuroimmunology, Max Planck Institute for Neurobiology, Martinsried, 2 Department of Neurology and Institute for Clinical Neuroimmunology, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany
Correspondence to:
Dr C. Linington, Department of Neuroimmunology, Max Planck Institute for Neurobiology, Am Klopferspitz 18A, D-82152 Martinsried, Germany E-mail: lining{at}neuro.mpg.de
We report a comparative study of the B- and T-cell responses to the extracellular immunoglobulin (Ig)-like domain of human myelin–oligodendrocyte glycoprotein (MOGIgd) in the blood of patients with multiple sclerosis and healthy controls using a bacterial recombinant human protein (rhMOGIgd). The frequency of anti-rhMOGIgd-seropositive samples, as determined by Western blotting, was significantly higher in the multiple sclerosis group (54%) than in normal random controls (excluding laboratory workers exposed to MOG) (22%; P = 0.02). In contrast, there was no difference in rhMOGIgd-induced proliferation indices of peripheral blood T cells between patients and controls. To characterize the rhMOGIgd-reactive T-cell repertoire, we isolated a panel of MOG-specific CD4+ T-cell lines from multiple sclerosis patients and normal subjects, and these revealed a heterogeneous response with respect to epitope specificity, cytokine response, MHC (major histocompatibility complex) restriction and T-cell receptor Vß-chain usage. The majority of the T-cell lines recognized epitopes in the N-terminal region of MOG (amino acids 1–60). One epitope (represented by peptide 27–50) was exclusively recognized by T-cell lines from normal controls. Forty per cent of the MOG-specific T-cell lines analysed displayed a Th-2 or Th-0 cytokine profile and could therefore act as helper T cells in vivo.
multiple sclerosis; autoantibodies; myelin–oligodendrocyte glycoprotein (MOG); T lymphocytes
CD = cluster of differentiation; EAE = experimental autoimmune encephalomyelitis; FACS = fluorescence-activated cell sorter; HLA = human leucocyte antigen; IFN = interferon; Ig = immunoglobulin; IL = interleukin; mAb = monoclonal antibody; MBP = myelin basic protein; MHC = major histocompatibility complex; MOG = myelin–oligodendrocyte glycoprotein; MOGIgd = immunoglobulin-like domain of MOG; PBMC = peripheral blood-derived mononuclear cell; pCP = primary chronic progressive; rh = recombinant human; rr = recombinant rat; RR = relapsing–remitting; sCP = secondary chronic progressive; TCR = T-cell receptor
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