@article{BergfeldDasariWerneretal.2017,
  author    = {Bergfeld, Arne and Dasari, Prasad and Werner, Sandra and Hughes, Timothy R. and Song, Wen-Chao and Hortschansky, Peter and Brakhage, Axel A. and H{\"u}nig, Thomas and Zipfel, Peter F. and Beyersdorf, Niklas},
  title     = {Direct binding of the pH-regulated Protein 1 (Pra1) from Candida albicans inhibits cytokine secretion by mouse CD4\(^{+}\) T cells},
  series = {Frontiers in Microbiology},
  volume    = {8},
  journal   = {Frontiers in Microbiology},
  number    = {844},
  doi       = {10.3389/fmicb.2017.00844},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158274},
  year      = {2017},
  abstract  = {Opportunistic infections with the saprophytic yeast Candida albicans are a major cause of morbidity in immunocompromised patients. While the interaction of cells and molecules of innate immunity with C. albicans has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by C. albicans. In particular, direct interaction of proteins secreted by C. albicans with CD4\(^{+}\) T cells has not been studied in detail. In a first screening approach, we identified the pH-regulated antigen 1 (Pra1) as a molecule capable of directly binding to mouse CD4\(^{+}\) T cells in vitro. Binding of Pra1 to the T cell surface was enhanced by extracellular Zn\(^{2+}\) ions which Pra1 is known to scavenge from the host in order to supply the fungus with Zn\(^{2+}\). In vitro stimulation assays using highly purified mouse CD4\(^{+}\) T cells showed that Pra1 increased proliferation of CD4\(^{+}\) T cells in the presence of plate-bound anti-CD3 monoclonal antibody. In contrast, secretion of effector cytokines such as IFNγ and TNF by CD4\(^{+}\) T cells upon anti-CD3/ anti-CD28 mAb as well as cognate antigen stimulation was reduced in the presence of Pra1. By secreting Pra1 C. albicans, thus, directly modulates and partially controls CD4\(^{+}\) T cell responses as shown in our in vitro assays.},
  language  = {en}
}
@article{MedlerNelkeWeisenbergeretal.2019,
  author    = {Medler, Juliane and Nelke, Johannes and Weisenberger, Daniela and Steinfatt, Tim and Rothaug, Moritz and Berr, Susanne and H{\"u}nig, Thomas and Beilhack, Andreas and Wajant, Harald},
  title     = {TNFRSF receptor-specific antibody fusion proteins with targeting controlled FcγR-independent agonistic activity},
  series = {Cell Death \& Disease},
  volume    = {10},
  journal   = {Cell Death \& Disease},
  doi       = {10.1038/s41419-019-1456-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223948},
  year      = {2019},
  abstract  = {Antibodies specific for TNFRSF receptors that bind soluble ligands without getting properly activated generally act as strong agonists upon FcγR binding. Systematic analyses revealed that the FcγR dependency of such antibodies to act as potent agonists is largely independent from isotype, FcγR type, and of the epitope recognized. This suggests that the sole cellular attachment, achieved by Fc domain-FcγR interaction, dominantly determines the agonistic activity of antibodies recognizing TNFRSF receptors poorly responsive to soluble ligands. In accordance with this hypothesis, we demonstrated that antibody fusion proteins harboring domains allowing FcγR-independent cell surface anchoring also act as strong agonist provided they have access to their target. This finding defines a general possibility to generate anti-TNFRSF receptor antibodies with FcγR-independent agonism. Moreover, anti-TNFRSF receptor antibody fusion proteins with an anchoring domain promise superior applicability to conventional systemically active agonists when an anchoring target with localized disease associated expression can be addressed.},
  language  = {en}
}