![]() Furthermore, they may confer pathogenic immune responses in autoimmune disorders such as multiple sclerosis, psoriasis vulgaris, rheumatoid arthritis, type I diabetes, inflammatory bowel disease and others. T cells are essential for protective immunity against infections and malignant tumors. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. There are no further patents, products in development or marketed products to declare. Nat Medicine in press, cited as reference 26.). (2012) Unbiased identification of target antigens of CD8+ T cells with combinatorial libraries coding for short peptides. The publication of the technology for the combinatorial peptide library is currently in press (Siewert K, Malotka J, Kawakami N, Wekerle H, Hohlfeld R, et al. This patent deals with a method to identify T cell antigens presented by HLA-class I molecules using a newly developed technology of combinatorial peptide libraries. The primer set for the amplification of TCR beta-chain rearrangements from single T cells is part of an international patent application (PCT/EP2011/063538) called Identification of T cell target antigens. Prinz declare that a patent application describing the technology has been filed. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have the following conflicts: Dr. Dornmair) and the German Academic Exchange Service (to Dr. Backes), the Deutsche Multiple Sklerose Gesellschaft (to Dr. Prinz), the Studienstiftung des Deutschen Volkes (to Dr. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This study was supported by the Deutsche Forschungsgemeinschaft through grants SFB-571-A1 and -A2 (to Dr. Received: MaAccepted: ApPublished: May 23, 2012Ĭopyright: © 2012 Kim et al. (2012) Analysis of the Paired TCR α- and β-chains of Single Human T Cells. It should facilitate essential new insights into the mechanisms of protective and pathologic immunity in many human T-cell mediated conditions and allow for resurrecting functional TCRs from any αβ-T cell of choice that can be used for investigating their specificity.Ĭitation: Kim S-M, Bhonsle L, Besgen P, Nickel J, Backes A, Held K, et al. These results show that our technology is an efficient instrument to analyse αβ-T cell responses with single cell resolution in man. In both diseases several clonally expanded T cells carried dual TCRs composed of one Vβ and two different Vα-chain rearrangements. An MS brain lesion contained two dominant CD8 + T-cell clones that extended over the white and grey matter and meninges. In PV, single cell TCR analysis of lesional T cells identified clonal CD8 + T cell expansions that predominated in the epidermis of psoriatic plaques. In both disorders we could detect various T cell clones as defined by multiple T cells with identical α- and β-chain rearrangements distributed across the tissue lesions. We validated our technology by the analysis of the pathologic T-cell infiltrates from tissue lesions of two T-cell mediated autoimmune diseases, psoriasis vulgaris (PV) and multiple sclerosis (MS). Here we describe a multiplex RT-PCR based technology, which for the first time allows for an unbiased analysis of the complete sequences of both α- and β-chains of TCR from single T cells. matching TCR α- and β-chain rearrangements of single human T cells is required for a precise investigation of clonal diversity, tissue distribution and specificity of protective and pathologic T-cell mediated immune responses.
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