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- Pasetto, A, et al.
(författare)
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Generation of T-cell receptors targeting a genetically stable and immunodominant cytotoxic T-lymphocyte epitope within hepatitis C virus non-structural protein 3
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93:Pt 2, s. 247-258
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis C virus (HCV) is a major cause of severe liver disease, and one major contributing factor is thought to involve a dysfunction of virus-specific T-cells. T-cell receptor (TCR) gene therapy with HCV-specific TCRs would increase the number of effector T-cells to promote virus clearance. We therefore took advantage of HLA-A2 transgenic mice to generate multiple TCR candidates against HCV using DNA vaccination followed by generation of stable T-cell–BW (T-BW) tumour hybrid cells. Using this approach, large numbers of non-structural protein 3 (NS3)-specific functional T-BW hybrids can be generated efficiently. These predominantly target the genetically stable HCV genotype 1 NS31073–1081 CTL epitope, frequently associated with clearance of HCV in humans. These T-BW hybrid clones recognized the NS31073 peptide with a high avidity. The hybridoma effectively recognized virus variants and targeted cells with low HLA-A2 expression, which has not been reported previously. Importantly, high-avidity murine TCRs effectively redirected human non-HCV-specific T-lymphocytes to recognize human hepatoma cells with HCV RNA replication driven by a subgenomic HCV replicon. Taken together, TCR candidates with a range of functional avidities, which can be used to study immune recognition of HCV-positive targets, have been generated. This has implications for TCR-related immunotherapy against HCV.
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- Mazzotti, L, et al.
(författare)
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T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:15
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Tidskriftsartikel (refereegranskat)abstract
- The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Here, we provide an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers’ choice through the multitude of available options. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago.
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- Rodriguez, L. F., et al.
(författare)
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Limits to the magnetic field in the planetary nebula NGC 246 from faraday rotation
- 2017
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Ingår i: Revista Mexicana de Astronomia y Astrofisica. - 0185-1101. ; 53:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- We present radio continuum observations of the linearly polarized extragalactic source J0047-1150, whose line of sight traverses the galactic planetary nebula NGC 246. We determine the position angle of the electric vector at seven frequencies between 1.3 and 1.8 GHz, finding no evidence of Faraday rotation and setting a 4-sigma upper limit to the rotation measure of 9.6 rad m(-2), which implies an upper limit to the average line-of-sight component of the magnetic field in NGC 246 of 1.3 mu G. However, we show that the rotation measure across a source with a dipolar magnetic field morphology practically cancels out. Therefore, if the magnetic field has this morphology, the local values of the magnetic field in NGC 246 could be much larger and will not be evident in a Faraday rotation experiment.
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