Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein.
We report a comparative study of the B- and T-cell responses to the extracellular immunoglobulin (Ig)-like domain of human myelin-oligodendrocyte glycoprotein (MOG(Igd)) in the blood of patients with multiple sclerosis and healthy controls using a bacterial recombinant human protein (rhMOG(Igd)). The frequency of anti-rhMOG(Igd)-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 rhMOG(Igd)-induced proliferation indices of peripheral blood T cells between patients and controls. To characterize the rhMOG(Igd)-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 Vbeta-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.
Lindert
R B
RB
Department of Neuroimmunology, Max Planck Institute for Neurobiology, Martinsried, Germany.
Haase
C G
CG
Brehm
U
U
Linington
C
C
Wekerle
H
H
Hohlfeld
R
R
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D018604:Epitope Mapping; D005110:Extracellular Space / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008285:Major Histocompatibility Complex / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D001323:Autoantibodies; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4; D007371:Interferon-gamma