Intrathecal CD4+ and CD8+ T‐cell responses to endogenously synthesized candidate disease‐associated human autoantigens in multiple sclerosis patients. Issue 2 (9th November 2015)

• Record Type: Journal Article
• Authors: van Nierop, Gijsbert P.; Janssen, Malou; Mitterreiter, Johanna G.; van de Vijver, David A.M.C.; de Swart, Rik L.; Haagmans, Bart L.; Verjans, Georges M.G.M.; Hintzen, Rogier Q.
• Is Part Of: European journal of immunology. Volume 46:Issue 2(2016)
• Page Start: 347
• Page End: 353
• Publication Date: 2015-11-09
• Subjects: Autoantigen -- Clinically isolated syndrome -- Cerebrospinal fluid -- Multiple sclerosis -- T cell; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201545921
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : MS pathology is potentially orchestrated by autoreactive T cells, but the antigens recognized remain unknown. A novel APC/T‐cell platform was developed to determine intrathecal CD4 + and CD8 + T‐cell responses to candidate MS‐associated autoantigens (cMSAg) in clinically isolated syndrome (CIS, n = 7) and MS ( n = 6) patients. Human cMSAg encoding open reading frames ( n = 8) were cloned into an Epstein–Barr virus (EBV)‐based vector to express cMSAg at high levels in EBV‐transformed B‐cells (BLCLs). Human cMSAg cloned were myelin‐associated and ‐oligodendrocyte glycoprotein, myelin basic protein, proteolipid protein, ATP‐dependent potassium channel ATP‐dependent inwards rectifying potassium channel 4.1, S100 calcium‐binding protein B, contactin‐2, and neurofascin. Transduced BLCLs were used as autologous APC in functional T‐cell assays to determine cMSAg‐specific T‐cell frequencies in cerebrospinal fluid derived T‐cell lines (CSF‐TCLs) by intracellular IFN‐γ flow cytometry. Whereas all CSF‐TCL responded strongly to mitogenic stimulation, no substantial T‐cell reactivity to cMSAg was observed. Contrastingly, measles virus fusion protein‐specific CD4 + and CD8 + T‐cell clones, used as control of the APC/T‐cell platform, efficiently recognized transduced BLCL expressing their cognate antigen. The inability to detect substantial T‐cell reactivity to eight human endogenously synthesized cMSAg in autologous APC do not support their role as prominent intrathecal T‐cell target antigens in CIS and MS patients early after onset of disease.