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

AI Article Synopsis

  • The text introduces T-FINDER, a new method for identifying T cell epitopes and their corresponding T cell receptors (TCRs) which is crucial for diagnostics and therapies.
  • T-FINDER combines sensitive TCR signaling with an antigen processing system to effectively detect unknown peptide:HLA ligands and validate TCR functionality against various targets.
  • The platform has been tested in several applications, including diffuse midline glioma, celiac disease, and rheumatoid arthritis, demonstrating its effectiveness and versatility in understanding immune responses.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10836725PMC
http://dx.doi.org/10.1126/sciadv.adk3060DOI Listing

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