Cerebrospinal fluid T cell clones from patients with multiple sclerosis: recognition of idiotopes on monoclonal IgG secreted by autologous cerebrospinal fluid B cells.
Due to somatic recombination and hypermutation, Ig variable heavy (V(H)) and light (V(L)) regions contain unique immunogenic determinants, idiotopes (Id), which can stimulate T cells. To address the relevance of this in a human disease, monoclonal IgG (mAb)-secreting B cell clones were established from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS). HLA-DR-restricted CD4(+) T cell lines and clones from CSF of both patients specifically recognized autologous CSF mAb. The CSF T cell clones produced IFN-gamma; some also produced TNF-alpha, IL-10 and IL-5. V(H) and V(L) on the monoclonal IgG derived from CSF B cells expressed amino acid replacements due to somatic mutations. A T cell epitope was mapped to a V(H) framework region, where an amino acid replacement was critical for the T cell recognition. The finding of Id-specific T cells and Id-bearing B cells in the CSF indicates that they coexist within the diseased organ, and provide a basis for the study of Id-driven T-B cell collaboration in a human autoimmune disease.
Holmøy
Trygve
T
Institute of Immunology, Rikshospitalet University Hospital, and University of Oslo, Rikshospitalet, Oslo, Norway.
Fredriksen
Agnete Brunsvik
AB
Thompson
Keith Michael
KM
Hestvik
Anne Lise Karlsgot
AL
Bogen
Bjarne
B
Vartdal
Frode
F
D000328:Adult; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes