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Search Results: 1 - 10 of 2801 matches for " Bernhard Knapp "
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A recombinant hybrid protein as antigen for an anti-blood stage malaria vaccine: a study on the conservation of a protective component
Knapp, Bernhard;Nau, Uwe;Scherf, Artur;
Memórias do Instituto Oswaldo Cruz , 1992, DOI: 10.1590/S0074-02761992000700029
Abstract: recently we have shown that two hybrid proteins expressed in escherichia coli confer protective immunity to aotus monkeys against an experimental plasmodium falciparum infection (knapp et al., 1992). both hybrid proteins carry a sequence containing amino acids 631 to 764 of the serine stretch protein serp (knapp et al., 1989b). we have studied the diversity of this serp region in field isolates of p. falciparum. genomic dna was extracted from the blood of six donors from different endemic areas of brazil and west africa. the serp region encoding amino acids 630 to 781 was amplified by polymerase chain reaction (pcr) and sequenced. only conserved amino acid substitutions in maximally two positions of the analyzed serp fragment could be detected which supports the suitability of this serp region as a component of anti-blood stage malaria vaccine.
Early Relaxation Dynamics in the LC 13 T Cell Receptor in Reaction to 172 Altered Peptide Ligands: A Molecular Dynamics Simulation Study
Bernhard Knapp, Georg Dorffner, Wolfgang Schreiner
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064464
Abstract: The interaction between the T cell receptor and the major histocompatibility complex is one of the most important events in adaptive immunology. Although several different models for the activation process of the T cell via the T cell receptor have been proposed, it could not be shown that a structural mechanism, which discriminates between peptides of different immunogenicity levels, exists within the T cell receptor. In this study, we performed systematic molecular dynamics simulations of 172 closely related altered peptide ligands in the same T cell receptor/major histocompatibility complex system. Statistical evaluations yielded significant differences in the initial relaxation process between sets of peptides at four different immunogenicity levels.
Large Scale Characterization of the LC13 TCR and HLA-B8 Structural Landscape in Reaction to 172 Altered Peptide Ligands: A Molecular Dynamics Simulation Study
Bernhard Knapp ,James Dunbar,Charlotte M. Deane
PLOS Computational Biology , 2014, DOI: doi/10.1371/journal.pcbi.1003748
Abstract: The interplay between T cell receptors (TCRs) and peptides bound by major histocompatibility complexes (MHCs) is one of the most important interactions in the adaptive immune system. Several previous studies have computationally investigated their structural dynamics. On the basis of these simulations several structural and dynamical properties have been proposed as effectors of the immunogenicity. Here we present the results of a large scale Molecular Dynamics simulation study consisting of 100 ns simulations of 172 different complexes. These complexes consisted of all possible point mutations of the Epstein Barr Virus peptide FLRGRAYGL bound by HLA-B*08:01 and presented to the LC13 TCR. We compare the results of these 172 structural simulations with experimental immunogenicity data. We found that simulations with more immunogenic peptides and those with less immunogenic peptides are in fact highly similar and on average only minor differences in the hydrogen binding footprints, interface distances, and the relative orientation between the TCR chains are present. Thus our large scale data analysis shows that many previously suggested dynamical and structural properties of the TCR/peptide/MHC interface are unlikely to be conserved causal factors for peptide immunogenicity.
Relaxation Estimation of RMSD in Molecular Dynamics Immunosimulations
Wolfgang Schreiner,Rudolf Karch,Bernhard Knapp,Nevena Ilieva
Computational and Mathematical Methods in Medicine , 2012, DOI: 10.1155/2012/173521
Abstract: Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of “lagged RMSD-analysis” as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged.
A Comparative Approach Linking Molecular Dynamics of Altered Peptide Ligands and MHC with In Vivo Immune Responses
Bernhard Knapp,Ulrich Omasits,Wolfgang Schreiner,Michelle M. Epstein
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011653
Abstract: The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood.
PeptX: Using Genetic Algorithms to optimize peptides for MHC binding
Bernhard Knapp, Verena Giczi, Reiner Ribarics, Wolfgang Schreiner
BMC Bioinformatics , 2011, DOI: 10.1186/1471-2105-12-241
Abstract: Since a full screening of all possible peptides is not feasible in reasonable runtime, we introduce a heuristic approach. We developed a framework for Genetic Algorithms to optimize peptides for the binding to major histocompatibility complexes. In an extensive benchmark we tested various operator combinations. We found that (1) selection operators have a strong influence on the convergence of the population while recombination operators have minor influence and (2) that five different binding prediction methods lead to five different sets of "optimal" peptides for the same major histocompatibility complex. The consensus peptides were experimentally verified as high affinity binders.We provide a generalized framework to calculate sets of high affinity binders based on different previously published scoring functions in reasonable runtime. Furthermore we give insight into the different behaviours of operators and scoring functions of the Genetic Algorithm.Antigen presenting cells (APCs) present peptides via their major histocompatibility complex (MHC) to T cell receptors (TCRs) of T cells which play an essential role in the adaptive immune system [1]. Before any recognition between T cell and APC can take place the peptides need to be processed within the APC and afterwards presented in a stable way on the cell surface of the APC. For most of these steps ample prediction methods exist [2-5]. In this context the binding prediction between MHC and the presented peptides is usually referred as T cell epitope prediction. In a usual workflow one wants to test different peptides or even possible fragments of a whole protein for its binding affinity to a given MHC. After this rough pre-selection step the most promising candidates are then tested in wet-lab experiments for their definitive binding affinity and applicability. The success rate of these approaches is discussed abundantly in the literature: While it is known that there is still much space for improvement of B ce
Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background
Knapp Bernhard,Fischer Gottfried,Van Hemelen Dries,Fae Ingrid
BMC Immunology , 2012, DOI: 10.1186/1471-2172-13-43
Abstract: Background Mugwort pollen allergens represent the main cause of pollinosis in late summer. The major allergen, Art v 1, contains only one single immunodominant, solely HLA-DR-restricted T cell epitope (Art v 125-36). The frequency of HLA-DRB1*01 is highly increased in mugwort-allergic individuals and HLA-DR1 serves as restriction element for Art v 125-36. However, Art v 125-36 also binds to HLA-DR4 with high affinity and DR1-restricted Art v 125-36 -specific T cell receptors can be activated by HLA-DR4 molecules. To understand the predominance of HLA-DR1 in mugwort allergy in spite of the degeneracy in HLA/peptide-binding and TCR-recognition, we investigated the molecular background of Art v 125-36 /MHC/TCR interactions in the context of HLA-DR1 compared to -DR4. Results The majority of Art v 125-36 -specific T cell lines and clones from HLA-DR1 carrying, mugwort pollen-allergic donors reacted to synthetic and naturally processed Art v 1–peptides when presented by HLA-DR1 or HLA-DR4 expressing antigen presenting cells. However, at limiting peptide concentrations DR1 was more effective in T cell stimulation. In addition, the minimal epitope for 50% of Art v 125-36 -specific T cells was shorter for DR1 than for DR4. In vitro binding assays of Art v 125-36 mutant peptides to isolated DR1- and DR4-molecules indicated similar binding capacities and use of the same register. In silico simulation of Art v 125-36 binding to HLA-DR1 and -DR4 suggested similar binding of the central part of the peptide to either molecule, but a higher flexibility of the N- and C-terminal amino acids and detachment at the C-terminus in HLA-DR1. Conclusions The predominance of HLA-DR1 in the response to Art v 125-36 may be explained by subtle conformation changes of the peptide bound to DR1 compared to DR4. Computer simulation supported our experimental data by demonstrating differences in peptide mobility within the HLA-DR complex that may influence TCR-binding. We suggest that the minor differences observed in vitro may be more relevant in the microenvironment in vivo, so that only presentation by HLA-DR1, but not -DR4 permits successful T cell activation.
Examining Variable Domain Orientations in Antigen Receptors Gives Insight into TCR-Like Antibody Design
James Dunbar,Bernhard Knapp,Angelika Fuchs,Jiye Shi,Charlotte M. Deane
PLOS Computational Biology , 2014, DOI: doi/10.1371/journal.pcbi.1003852
Abstract: The variable domains of antibodies and T-Cell receptors (TCRs) share similar structures. Both molecules act as sensors for the immune system but recognise their respective antigens in different ways. Antibodies bind to a diverse set of antigenic shapes whilst TCRs only recognise linear peptides presented by a major histocompatibility complex (MHC). The antigen specificity and affinity of both receptors is determined primarily by the sequence and structure of their complementarity determining regions (CDRs). In antibodies the binding site is also known to be affected by the relative orientation of the variable domains, VH and VL. Here, the corresponding property for TCRs, the Vβ-Vα orientation, is investigated and compared with that of antibodies. We find that TCR and antibody orientations are distinct. General antibody orientations are found to be incompatible with binding to the MHC in a canonical TCR-like mode. Finally, factors that cause the orientation of TCRs and antibodies to be different are investigated. Packing of the long Vα CDR3 in the domain-domain interface is found to be influential. In antibodies, a similar packing affect can be achieved using a bulky residue at IMGT position 50 on the VH domain. Along with IMGT VH 50, other positions are identified that may help to promote a TCR-like orientation in antibodies. These positions should provide useful considerations in the engineering of therapeutic TCR-like antibodies.
Method and Apparatus for Creating Problem-Solving Complexes from Individual Elements  [PDF]
Bernhard Mitterauer
Advances in Bioscience and Biotechnology (ABB) , 2014, DOI: 10.4236/abb.2014.54038
Abstract:

Based on the biological key-lock-principle common in various biological systems such as the human brain, this paper relates to a method and device for creating problem-solving complexes from individual elements that can be coupled with one another and that have different properties to solve problems. The problem solution can be carried out either serially with a large computer, or with several independent, hierarchically joined computers. In this system, an independent control unit that assumes a multitude of tasks and also acts as an interface with access to all participating computers, is assigned to each problem or object class according to the amount of potential problem-oriented solutions. Such a unit prepares the partial solutions found in its computer for the totality of the solutions computed in the associated computers, finally leading to a total problem solution.

Rarity, Species Richness, and the Threat of Extinction—Are Plants the Same as Animals?
Sandra Knapp
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001067
Abstract: Assessment of conservation status is done both for areas or habitats and for species (or taxa). IUCN Red List categories have been the principal method of categorising species in terms of extinction risk, and have been shown to be robust and helpful in the groups for which they have been developed. A recent study highlights properties associated with extinction risk in flowering plants, focusing on the species-rich hot spot of the Cape region of South Africa, and concludes that merely following methods derived from studies of vertebrates may not provide the best estimates of extinction risk for plants. Biology, geography, and history all are important factors in risk, and the study poses many questions about how we categorise and assess species for conservation priorities.
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