After encounter with a central nervous system (CNS)-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1) rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J) mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

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Sulfurtransferases/rhodaneses (Str) are enzymes widely distributed in archaea, prokaryota and eukaryota, and catalyze the transfer of sulfur from a donor molecule to a thiophilic acceptor substrate. In this reaction, Str cycles between the sulfur-free and the sulfur-substituted form. Two-domain Str consist of two globular domains of nearly identical size and conformation connected by a short linker sequence, which is elongated in plant two-domain Str proteins compared to Str in other organisms. The two-domain Arabidopsis thaliana Str1 protein (At1g 79230) was expressed in Escherichia coli as a mature protein, as a variant without the elongated linker sequence, and as AtStr1C332S and AtStr1C339V. The persulfuration state of the purified recombinant proteins was investigated in the presence and absence of sulfur donors by fluorescence spectroscopy. The secondary structure was analyzed by circular dichroism (CD) in the far-UV range, while overall changes in tertiary structure were determined by CD in the near-UV range. Finally, protein stability was analyzed by tryptic digestion. The elongated linker sequence is essential for correct conformation and stability, and thereby affects the catalytic activity of AtStr1. Replacement of the catalytic cysteine residue C332 leads to higher rigidity of the molecule, whereas replacement of C339 does not lead to any conformational changes, providing evidence of the direct involvement of C339 in catalysis.