T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery
Schmid, T.; Cetin, M.; Pinamonti, V.; Fuentes, A. M.; Kromer, K.; Lerner, T.; Zhang, J.; Boschert, T.; Herzig, Y.; Ehlert, C.; Fisch, L.; Dragan, V.; Kouwenhoven, A.; Van Schoubroeck, B.; Wils, H.; Van Hove, C.; Platten, M.; Green, E. W.; Stevenaert, F.; Felix, N.; Lindner, J. M.
Show 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. Addressing this bottleneck, we established T-FINDER (T cell Functional Identification and (Neo)-antigen Discovery of Epitopes and Receptors), a platform that rapidly deconvolutes CD4 and CD8 TCR reactivities to targets physiologically processed and presented by an individuals unmanipulated, complete HLA haplotype. By using a highly sensitive TCR signaling reporter capable of detecting even low-affinity TCR:ligand interactions, T-FINDER not only robustly identifies unknown peptide:HLA ligands from complex antigen libraries, but also rapidly screens and functionally validates the specificity of complex TCR libraries against known or predicted targets. To demonstrate its pan-HLA presentation capacity, we apply the platform to multiple TCR-based applications, including glioma, celiac disease, and rheumatoid arthritis, providing unique biological insights and showcasing T-FINDERs potency and versatility.
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