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Träfflista för sökning "WFRF:(Winkler Christoph K.) srt2:(2020)"

Sökning: WFRF:(Winkler Christoph K.) > (2020)

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1.
  • Bartsch, Yannic C, et al. (författare)
  • IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants
  • 2020
  • Ingår i: The Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 146:3, s. 652-666
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Effector functions of IgG antibodies (Abs) are regulated by their Fc N-glycosylation pattern. IgG Fc glycans that lack galactose and terminal sialic acid residues correlate with the severity of inflammatory (auto)immune disorders and have also been linked to the protection against viral infection and discussed in the context of vaccine-induced protection. In contrast, sialylated IgG Abs have shown immunosuppressive effects.OBJECTIVE: We sought to investigate IgG glycosylation programming during the germinal center (GC) reaction upon immunization of mice with a foreign protein antigen and different adjuvants.METHODS: Mice were analyzed for GC T, B cell and plasma cell responses as well as antigen-specific serum IgG subclass titers and Fc glycosylation patterns.RESULTS: Different adjuvants induce distinct IgG+ GC B cell responses with specific transcriptomes and expression levels of the α2,6-sialyltransferase responsible for IgG sialylation that correspond to distinct serum IgG Fc glycosylation patterns. Low IgG Fc sialylation programming in GC B cells was overall highly dependent on the T follicular helper (TFH) cell-inducing cytokine IL-6, especially induced by water-in-oil adjuvants and Mycobacterium tuberculosis (Mtb). Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27R-dependent IFNγ+ TFH1 cells, IL-6/IL-23-dependent IL-17A+ TFH17 cells and high TFH/T follicular regulatory (TFR) cell ratios. The two latter were here dependent on Mtb and its cord factor.CONCLUSION: These findings on adjuvant-dependent GC responses and IgG glycosylation programming may aid the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns.
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2.
  • Jost, Etta, et al. (författare)
  • Variants of the Acyltransferase from Mycobacterium smegmatis Enable Enantioselective Acyl Transfer in Water
  • 2020
  • Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 10:18, s. 10500-10507
  • Tidskriftsartikel (refereegranskat)abstract
    • The acyltransferase from Mycobacterium smegmatis (MsAcT) complements the well-established acylation activity of hydrolases in organic solvents with its activity to perform acylation reactions (among other reactions) in an aqueous environment. The enzyme’s potential is however limited, due to its poor regio- and stereoselectivity with enantioselectivities (E-values) below 20 for bulky (aromatic) substrates. By applying computer-guided rational design, a library of single variants was designed that allowed conversion of a set of previously challenging substrates with good activity and E-values up to >200. The computational predictions were found to be in agreement with experimental data, which in turn allowed for the generation of even more active and selective double variants. Overall, the produced set of variants provides a toolbox for the enantioselective acylation of challenging alcohols in water, effectively contributing to an alternative to reactions in organic solvents.
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