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

Abstract:

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.

SEEK ID: https://publications.h-its.org/publications/1783

DOI: 10.1126/sciadv.adk3060

Research Groups: Computational Carbon Chemistry

Publication type: Journal

Journal: Science Advances

Citation: Sci. Adv. 10(5),eadk3060

Date Published: 2nd Feb 2024

Registered Mode: by DOI

Authors: 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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Citation
Cetin, M., Pinamonti, V., Schmid, T., Boschert, T., Mellado Fuentes, A., Kromer, K., Lerner, T., Zhang, J., Herzig, Y., Ehlert, C., Hernandez-Hernandez, M., Samaras, G., Torres, C. M., Fisch, L., Dragan, V., Kouwenhoven, A., Van Schoubroeck, B., Wils, H., Van Hove, C., … Lindner, J. M. (2024). T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery. In Science Advances (Vol. 10, Issue 5). American Association for the Advancement of Science (AAAS). https://doi.org/10.1126/sciadv.adk3060
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Created: 9th Feb 2024 at 11:16

Last updated: 5th Mar 2024 at 21:25

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