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

Autor:	Cetin M; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Pinamonti V; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany., Schmid T; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Boschert T; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Helmoltz Institute for Translational Oncology (HI-TRON), Heidelberg, Germany., Mellado Fuentes A; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Kromer K; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany., Lerner T; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Zhang J; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Herzig Y; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Ehlert C; Heidelberg Institute for Theoretical Studies (HITS gGmbH), 69118 Heidelberg, Germany., Hernandez-Hernandez M; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Samaras G; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Torres CM; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany., Fisch L; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany., Dragan V; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany., Kouwenhoven A; Janssen Research and Development, Beerse, Belgium., Van Schoubroeck B; Janssen Research and Development, Beerse, Belgium., Wils H; Janssen Research and Development, Beerse, Belgium., Van Hove C; Janssen Research and Development, Beerse, Belgium., Platten M; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Helmoltz Institute for Translational Oncology (HI-TRON), Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany., Green EW; DKTK CCU Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, MCTN Heidelberg University, Mannheim, Germany., Stevenaert F; Janssen Research and Development, Beerse, Belgium., Felix NJ; Janssen Research and Development, Spring House, PA, USA., Lindner JM; BioMed X GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2024 Feb 02; Vol. 10 (5), pp. eadk3060. Date of Electronic Publication: 2024 Feb 02.
DOI:	10.1126/sciadv.adk3060
Abstrakt:	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.
Databáze:	MEDLINE
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