T Cells from Multiple Sclerosis Patients Recognize Multiple Epitopes on Self-IgG

• Published in: Scandinavian journal of immunology Vol. 66; no. 4; pp. 393 - 401
• Main Authors: Hestvik, A.L.K, Vartdal, F, Fredriksen, A.B, Thompson, K.M, Kvale, E.O, Skorstad, G, Bogen, B, Holmoy, T
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2007; Blackwell Publishing Ltd
• Subjects: Adult; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Complementarity Determining Regions - immunology; Epitopes, T-Lymphocyte - immunology; Female; HLA Antigens - immunology; HLA-DR Antigens - immunology; HLA-DRB1 Chains; Humans; Immunoglobulin G - immunology; Immunoglobulin Idiotypes - immunology; Immunoglobulin Variable Region - genetics; Immunoglobulin Variable Region - immunology; Interferon-gamma - immunology; Interleukins - immunology; Male; Multiple Sclerosis - blood; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - immunology; Peptide Fragments - immunology; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/j.1365-3083.2007.01955.x

The highly diversified variable regions of immunoglobulin (Ig) molecules contain immunogenic determinants denoted idiotopes. We have previously reported that T cells from multiple sclerosis (MS) patients recognize IgG from autologous cerebrospinal fluid (CSF), and mapped a T-cell epitope to an IgG idiotope. To test the ability of CSF IgG molecules to elicit a broad polyclonal T-cell response in MS, we have analysed T-cell responses in the blood and CSF against idiotope peptides spanning complementarity determining region (CDR) 3 and somatic mutations within the variable regions of monoclonal CSF IgG. Consistent with a diversified idiotope-specific T-cell repertoire, CD4⁺ T cells from both patients recognized several idiotope peptides presented by HLA-DR molecules. Mutations were critical for T-cell recognition, as T cells specific for a mutated CDR1 peptide did not recognize corresponding germline-encoded peptides. One T-cell clone recognized both an idiotope peptide and the B-cell clone expressing this idiotope, compatible with endogenous processing and presentation of this idiotope by B cells. These results suggest that mutated CSF IgG from MS patients carry several T-cell epitopes, which could mediate intrathecal IgG production and inflammation in MS through idiotope-driven T-B-cell collaboration.