1,164 research outputs found
Code: Predicting T Cell Receptor Functionality against Mutant Epitopes
No full text<p>This upload contains the Code for "Predicting T Cell Receptor Functionality against Mutant Epitopes" (DOI: https://doi.org/10.1101/2023.05.10.540189) by Felix Drost, Emilio Dorigatti, Adrian Straub, Philipp Hilgendorf, Karolin I. Wagner, Kersten Heyer, Marta López Montes, Bernd Bischl, Dirk H. Busch, Kilian Schober, and Benjamin Schubert.</p>
Dataset: Predicting T Cell Receptor Functionality against Mutant Epitopes
No full text<p>This upload contains the Datasets and Supplementary Material for "Predicting T Cell Receptor Functionality against Mutant Epitopes" (DOI: https://doi.org/10.1101/2023.05.10.540189) by Felix Drost, Emilio Dorigatti, Adrian Straub, Philipp Hilgendorf, Karolin I. Wagner, Kersten Heyer, Marta López Montes, Bernd Bischl, Dirk H. Busch, Kilian Schober, and Benjamin Schubert.</p>
Formal Techniques and Self/Other Relations in the Novels of Dirk Bogarde
No full textThe thesis foregrounds the distinctive contribution Dirk Bogarde made to
contemporary writing in a second career that developed in parallel to his screen
commitments. It dispels the notion that Bogarde followed a familiar path as an actor
who wrote books. Instead it establishes his reputation as an innovative writer whose
formal technique was substantially influenced by the textual systems of cinema and
the cross-fertilisation from acting to writing.
In examining the formative factors that steered Bogarde towards authorship, the
thesis addresses the role of performance as a generative factor in the evolution of the
novels, establishing a discursive link with Bakhtinian dialogism, and specifically,
transgredience as a formal imperative. Secondly, it affords a critical insight into why
the major concerns with staging and performativity preoccupy his writing career.
The thesis claims that Bogarde was an empirically dialogical writer whose use
of camera-eye narration fostered the proliferation of competing discourses across the
fiction. This formal dynamic is centred on the relationship between stages and
dialogism, which incorporates the work of Erving Goffinan as a complementary
critique to Bakhtinian theory with its emphasis on self-presentation. The concern
with socially-constructed behaviour leads the thesis to address the associated issues of
stereotyping and 'otherness', which in terms of body politics is articulated by the
mono logic drive to confine the sexual 'other' to a fixed representation.
Bogarde's ability to draw on cinematic and performance techniques identifies
an area of expertise unavailable to most other writers. This is an unusual repository
of skills to bring to writing which is why the thesis makes the claim for his singular
achievement as a contemporary author. There are fruitful points of intersection to be
explored in this respect with the work of Christopher Isherwood, whom Bogarde read
and admired, as a basis for further research. It is hoped that the thesis will play its
part in opening up new possibilities for Bogarde's writing to be re-visited by future
critics
Reform der Polizeigesetze
No full textBusch H, Espin Grau H, Lampe D, eds. Reform der Polizeigesetze. Kriminologisches Journal. 2020;52(2)
Editorial. Zur Einführung in das Themenheft "Reform der Polizeigesetze"
No full textBusch J, Espin Grau H, Lampe D. Editorial. Zur Einführung in das Themenheft "Reform der Polizeigesetze". Kriminologisches Journal : Krim J . 2020;52(2):87-96
Role of CD28 for the generation and expansion of antigen-specific CD8(+) T lymphocytes during infection with Listeria monocytogenes
No full textAcknowledgments
We thank Drs. Tak W. Mak, Eric Pamer, Dirk Busch, and John Altman for providing material and valuable suggestions and Ralf Winter, Karin Bordasch, and Manuela Stäber for their excellent technical assistance
Development of murine Fab-Multimers for selection and functional characterization of reversibly stained regulatory T cells
No full textIn dieser Arbeit wurden, basierend auf Streptamer-Technologie, erstmals murine Fab-Multimere gegen CD4 und CD25 entwickelt, um regulatorische T-Zellen (Tregs) der Maus reversibel anfärben und anreichern zu können. Die neuen Reagenzien wurden mit konventioneller Antikörperfärbung verglichen und erzielten in durchflusszytometrischen Analysen zu Färbung, Reinheit und Spezifität stets gleichwertige oder bessere Ergebnisse. Zusätzlich lassen Suppressions- und Proliferationsanalysen sowie adoptive Zelltransfers auf eine tendenziell geringere funktionelle Beeinträchtigung reversibel gefärbter Tregs schließen. Diese Daten können dazu beitragen, Tregs zelltherapeutisch besser nutzbar zu machen.In this dissertation, for the first time murine Fab-multimers against CD4 and CD25 were developed using Streptamer-technology to reversibly stain and enrich murine regulatory T cells (Tregs). The new reagents were compared to conventional antibody staining and analyzed by flow cytometry, obtaining equal or better results in staining qualities, purity and specificity. In addition suppression assays, proliferation experiments and adoptive cell transfer suggested a less functional impairment of reversibly stained Tregs. These data might contribute to bringing purified Tregs to clinical application
Transfer of the koff-rate-assay on CD8+ T cells from the murine to the human system
No full textIn dieser Arbeit wurde der koff-rate-Assay vom murinen auf das humane System übertragen. Der Assay ist eine neue Methode zur Messung der Dissoziationskinetiken von monomeren pMHCI-Molekülen von T-Zell-Rezeptoren (TCR) an lebenden CD8+ T-Zellen. Reversibel polymerisierte, fluoreszenzmarkierte pMHC-Moleküle binden stabil an TCR. Nach schlagartiger Monomerisierung diffundieren die pMHC-Moleküle mit messbaren Kinetiken von den TCR ab. Da der Assay nicht analog übertragen werden konnte, wurden die Probleme analysiert und ein Lösungsansatz entwickelt.In this work the koff-rate-assay has been transferred from the murine to the human setup. The assay is a new method to measure dissociation kinetics of monomeric pMHCI molecules from T cell receptors (TCR) on living CD8+ T cells. Reversibly polymerized, fluorescence-marked pMHC molecules bind stably to TCR. After sudden monomerization the pMHC molecules dissociate from the TCR with distinct kinetics that can be measured. Since an analogous transfer to the human system was not possible, the problems were analyzed and a new approach was developed
Formation and immunomodulatory function of meningeal B-cell aggregates in progressive CNS autoimmunity
No full textMeningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic Multiple Sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of Multiple Sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T cell- and B cell-receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of α4 integrins by antigen-specific T cells. T cell-conditional genetic ablation of α4 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with α4 integrin-sufficient T cells. B cell-conditional ablation of α4 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with α4 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20 percent of B cells in organised meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient therapies directed against meningeal B cell aggregates for clinical application in Multiple Sclerosis
Analyzing the development of adaptive immune responses derived from single naïve CD8+ T cells
No full textIn der vorliegenden Dissertation wurde die Entwicklung von CD8+ T-Zell-Immunantworten ausgehend von einzelnen naiven T-Zellen untersucht. Anzahl und Phänotyp der Nachkommen, die aus einzelnen T-Zellen hervorgingen variierte deutlich. Gemeinsam ergaben diese variablen Zellschicksale jedoch ein vorhersagbares, an das Infektionsgeschehen angepasstes Muster. Die Robustheit der CD8+ T-Zell-Immunantwort wird also nicht auf Ebene der einzelnen in die Immunantwort rekrutierten T-Zelle etabliert, sondern erst durch die Einbeziehung einer ausreichend großen naiven T-Zellpopulation gewährleistet.In the present dissertation development of CD8+ T cell immune responses derived from single naïve T cells was studied. Number and phenotype of offspring derived from a single naïve T cell varied considerably. However, together these varying single cell fates created predictable response patterns, tailored to fighting the infectious agent. Thus, robustness of CD8+ T cell immune responses is not established by individual naïve T cells but rather guaranteed by recruitment of naïve T cell populations
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