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T-FINDER: a highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery

Effective, unbiased, high-throughput methods to functionally identify both class II and class I HLA-presented T cell epitopes and their cognate T cell receptors (TCRs) are essential for and prerequisite to diagnostic and therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER...

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Main Authors: Cetin, Miray (Author) , Pinamonti, Veronica (Author) , Schmid, Theresa (Author) , Boschert, Tamara (Author) , Mellado Fuentes, Ana (Author) , Kromer, Kristina (Author) , Lerner, Taga (Author) , Zhang, Jing (Author) , Herzig, Yonatan (Author) , Ehlert, Christopher (Author) , Hernández, Miguel (Author) , Samaras, Georgios (Author) , Maldonado Torres, Clàudia (Author) , Fisch, Laura (Author) , Dragan, Valeriia (Author) , Kouwenhoven, Arlette (Author) , Van Schoubroeck, Bertrand (Author) , Wils, Hans (Author) , Van Hove, Carl (Author) , Platten, Michael (Author) , Green, Edward W. (Author) , Stevenaert, Frederik (Author) , Felix, Nathan J. (Author) , Lindner, John M. (Author)
Format: Article (Journal)
Language:English
Published: Feb 2024
In: Science advances
Year: 2024, Volume: 10, Issue: 5, Pages: 1-12
ISSN:2375-2548
DOI:10.1126/sciadv.adk3060
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1126/sciadv.adk3060
Verlag, kostenfrei, Volltext: https://www.science.org/doi/10.1126/sciadv.adk3060
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Author Notes:Miray Cetin, Veronica Pinamonti, Theresa Schmid, Tamara Boschert, Ana Mellado Fuentes, Kristina Kromer, Taga Lerner, Jing Zhang, Yonatan Herzig, Christopher Ehlert, Miguel Hernandez-Hernandez, Georgios Samaras, Claudia Maldonado Torres, Laura Fisch, Valeriia Dragan, Arlette Kouwenhoven, Bertrand Van Schoubroeck, Hans Wils, Carl Van Hove, Michael Platten, Edward W. Green, Frederik Stevenaert, Nathan J. Felix, John M. Lindner
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Summary:Effective, unbiased, high-throughput methods to functionally identify both class II and class I HLA-presented T cell epitopes and their cognate T cell receptors (TCRs) are essential for and prerequisite to diagnostic and therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER [T cell Functional Identification and (Neo)-antigen Discovery of Epitopes and Receptors], a system to rapidly deconvolute CD4 and CD8 TCRs and targets physiologically processed and presented by an individual’s unmanipulated, complete human leukocyte antigen (HLA) haplotype. Combining a highly sensitive TCR signaling reporter with an antigen processing system to overcome previously undescribed limitations to target expression, T-FINDER both robustly identifies unknown peptide:HLA ligands from antigen libraries and rapidly screens and functionally validates the specificity of large TCR libraries against known or predicted targets. To demonstrate its capabilities, we apply the platform to multiple TCR-based applications, including diffuse midline glioma, celiac disease, and rheumatoid arthritis, providing unique biological insights and showcasing T-FINDER’s potency and versatility.
Item Description:Online veröffentlicht: 02. Februar 2024
Gesehen am 21.08.2024
Physical Description:Online Resource
ISSN:2375-2548
DOI:10.1126/sciadv.adk3060

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