Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein

• Published in: Brain (London, England : 1878) Vol. 122; no. 11; pp. 2089 - 2100
• Main Authors: Lindert, Ralf-Björn, Haase, Claus G., Brehm, Uschi, Linington, Christopher, Wekerle, Hartmut, Hohlfeld, Reinhard
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-1999; Oxford Publishing Limited (England)
• Subjects: Amino Acid Sequence; Antigens, Surface - immunology; autoantibodies; Autoantibodies - blood; B-Lymphocytes - immunology; Biological and medical sciences; Blotting, Western; CD = cluster of differentiation; CD4-Positive T-Lymphocytes - immunology; Cell Division - physiology; Cell Line; EAE = experimental autoimmune encephalomyelitis; Epitope Mapping; Extracellular Space - metabolism; FACS = fluorescence-activated cell sorter; Flow Cytometry; HLA = human leucocyte antigen; Humans; IFN = interferon; Ig = immunoglobulin; IL = interleukin; Immunohistochemistry; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; mAb = monoclonal antibody; Major Histocompatibility Complex - immunology; MBP = myelin basic protein; Medical sciences; MHC = major histocompatibility complex; MOG = myelin–oligodendrocyte glycoprotein; MOGIgd = immunoglobulin-like domain of MOG; Molecular Sequence Data; multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Myelin Basic Protein - immunology; Myelin Proteins; Myelin-Associated Glycoprotein - immunology; Myelin-Oligodendrocyte Glycoprotein; myelin–oligodendrocyte glycoprotein (MOG); Neurology; PBMC = peripheral blood-derived mononuclear cell; pCP = primary chronic progressive; Receptors, Antigen, T-Cell, alpha-beta - metabolism; rh = recombinant human; rr = recombinant rat; RR = relapsing–remitting; sCP = secondary chronic progressive; T lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; TCR = T-cell receptor; Human; Nervous system diseases; Multiple sclerosis; Myelin; Glycoprotein; Autoantibody; Exploration; B-Lymphocyte; Inflammatory disease; Oligodendrocyte; Central nervous system disease; T-Lymphocyte; Immunoblotting assay
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/122.11.2089

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 Vβ-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.