Proteomanalyse humaner Glatiramerazetat und Myelin basisches Protein spezifischer T-Zell Linien von MS Patienten und gesunden Kontrollpersonen

Abstract

Protein expression profiling of human glatiramer acetate (GA) and myelin basic protein (MBP) specific T cell lines from a multiple sclerosis (MS) patient and healthy donors Investigations in MS and the animal model experimental autoimmune encephalomyelitis (EAE) indicate that autoreactive T cells play a pivotal role in the pathogenesis. Putative auto antigens include e.g. MBP. One approved therapy of patients with relapsing-remitting MS is GA (Copaxone®), which induces a shift in the phenotype of CD4+ T cells from TH1- to TH2-type. As the molecular mechanisms involved are largely unknown, we were interested in the regulated proteome of GA- and MBP-specific human T cell lines. We generated GA- and MBP-specific T cell lines from three healthy donors and GA- specific T cell lines from a MS patient before and after 6 months of GA therapy. Proteome analysis of activated and resting GA- and MBP-specific, CD3+ CD4+ CD8- T cells was done by SDS-PAGE and MALDI-TOF mass spectrometry. A total of 120 regulated protein spots were detected on the gels. 69 were identified as different proteins by mass spectrometry. A single protein pathway analysis of these proteins led us to five proteins. One of them is known to be a negative regulator of growth factors. Three proteins known for their anti-inflammatory properties were upregulated in GA-specific T cells, one protein with pro-inflammatory characteristics was found upregulated in encephalitogenic MBP-specific T cells. Based on their expression profile and their characteristics these proteins may be involved in immunological mechanisms relevant in MS and/or possibly during GA treatment.