Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 46 for “"affinity maturation"”.
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Affinity Maturation of Peptides to Bind Protein-Protein Interfaces
… combinatorial peptide libraries with label- free affinity selection platforms have been developed to study protein-ligand interactions. Applying this platform, several multi-alanine-substituted analogs with picomolar binding affinity were discovered for the oncogenic protein MDM2. In addition, …
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Selection Dynamics in the Germinal Center During Antibody Affinity Maturation
<p>The maturation of antibody affinity during the immune response, discovered as a serological phenomenon in 1964, is critical to the development of high affinity humoral immunity. This process takes place in germinal centers (GCs), which are microanatomical structures composed of antigen-specific …
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Modelling the affinity maturation of B lymphocytes in the germinal centre
… development of a computer model to simulate the affinity maturation of B lymphocytes in the germinal centre in 3-D because certain behavioural aspects cannot currently be examined experimentally. The software tool recreates the structure of the germinal centre that enables the B cells to move and …
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Affinity Maturation of the D1.3 Antibody Using Yeast Surface Display and Flow Cytometry
… methodologies were explored for improving YSD affinity maturation of anti-protein antibodies, using scFv D1.3. Using equilibrium sorted YSD with the D1.3/M3 antibodies, a single-pass enrichment factor of 125-fold (+/-65-fold) was achieved, indicating excellent differentiation between clones of …
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Hapten Binding by Lymphocyte Surface Immunoglobulin and the Subsequent Implications for Affinity Maturation
… immunoglobulin (smIg) in the elicitation of affinity maturation has been approached from a number of possible considerations. The salient features are summarized. First, retention time of antigen by membrane associated smIg involves assessment of geometric and probabilistic arguments, in …
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Interplay between Extra-Germinal Center expansion of memory B cells and affinity maturation during the humoral recall response
… response, GCs produce memory B cells with a high affinity for the infecting pathogen or vaccine antigen, but they also generate many low affinity memory B cells. During the recall response, the EGC plays a crucial role by selecting and expanding the best pre-existing memory B cells to the …
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Building a Genetic System in Yeast to Search for High Affinity Proteins in Sequence Space
… step in discovering new binders is called affinity maturation, when an initial hit that shows some ability to bind the target is further mutated in additional steps to improve binding affinity, specificity, solubility, pharmacokinetic profile. Ideally, the methods for affinity maturation …
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Engineering T Cell Receptors for Potential Therapeutic Applications
… strategies to allow for the isolation of high affinity mutants of many different TCRs was extended to methods for affinity maturation in Chapter 4. Previous affinity-based selections have involved incubating yeast cells with fluorescently labeled recombinant pepMHC ligand. Many pepMHC ligands …
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Biophysical characterization of high affinity engineered single chain Fv antibody fragments
High affinity antibody binding interactions are important for both pharmaceutical and biotechnological uses. However, designing higher affinity interactions has remained difficult. Both high affinity interactions from nature and the results from directed evolution affinity maturation processes may …
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The modulation of autoimmune disease progression in mouse models
… producing them have been through the process of affinity maturation. Activation-induced cytidine deaminase (AID) is a core enzyme that regulates somatic hypermutation (SHM) and class switch recombination (CSR), the two key mechanisms in affinity maturation. We showed that genetic ablation of AID …
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Mechanisms Underpinning Functional Resident Humoral Lung Immunity
… functionally competent and can support antibody affinity maturation is unknown. This project aims to elucidate key differences between classic and ectopic germinal centres which may inform how we can improve medical interventions to enhance humoral protection against autoimmunity and infectious …
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Replaying Life's Tape With Intraclonal Germinal Center Evolution
<p>Because high-affinity antibodies produced by germinal centers (GCs) are critical in protecting against the ever-increasing array of pathogens, understanding how GC response allows our immune system to recognize a variety of pathogens and develop specific and effective immunity against each …
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Investigating the Effect of Antibody-Mediated Feedback on Ongoing Germinal Center Responses
… immune memory in the form of long-lasting, high-affinity serum antibody titers, which requires the participation of B cells in the germinal center (GC) response. It is well-established that pre-existing antibodies can influence the outcome of future humoral responses; however, whether antibody …
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In Vitro Evolution of Antibody Affinity using Libraries with Insertions and Deletions
… (SHM) leads to antibodies with improved affinity and specificity. Sequence diversification by SHM is mainly achieved by introduction of point substitutions and a small percentage of insertions/deletions (indels). Although the percentage of indels in affinity matured antibodies is low, …
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Optimizing vaccine dosing kinetics for stronger antibody response
… This thesis investigates various aspects of affinity maturation that are relevant to vaccination and therapeutic strategies but are not yet fully understood mechanistically, ranging from the evolution of the heterogeneity of the antibody population with respect to affinity to optimal design …
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Opposing Actin Networks Modulate the Mechano-Activation of the Integrin LFA-1 During Immunological Synapse formation
… of conformational changes associated with affinity maturation at the IS. Furthermore I find that full induction of LFA-1 conformational change requires binding to immobilized ligand, and is enhanced through the induced fit of ligand binding, alongside the enhanced tension provided by …
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The Function of PTPN22 and the Autoimmune Risk Variant LypW in Immune Responses to Vaccination
High-affinity antibody production, T cell activation, and Interferon upregulation all contribute to protective immunity that occurs in humans following influenza immunization. Hematopoietic cell-specific PTPN22 encodes Lymphoid Phosphatase (Lyp), which regulates lymphocyte antigen receptor and …
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Dissecting the role of RNA helicase DDX3X in mRNA translation and B-cell function during immune responses
… structures are the primary sites of antibody affinity maturation and a common site of B-cell lymphomagenesis. Mutations in DEAD-box helicase 3X (DDX3X) have previously been found in B-cell lymphomas driven by the transcription factor MYC. Reduced DDX3X function buffers the effect of MYC on the …
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Recall Germinal Center and Antibody Responses
… antibodies that are of greater magnitude and affinity compared to those induced after primary exposure to antigen.The anamnestic nature of the response is a result of the recall of memory B cells (MBCs) that have undergone clonal expansion and affinity maturation in germinal centers(GCs) …
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Genetic engineering of antibody fragments for the detection of illicit drugs
… This thesis describes the production and affinity maturation of antibodies for the detection of illicit drugs and their application in ELISA, Biacore surface plasmon resonance -based biosensor assays and, finally, in a multidrug-based assay. The first phase of this work focused on the …
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