Faculty, Staff and Student Publications
Publication Date
5-2-2024
Journal
Cancer Immunology Research
Abstract
Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen derived from human papillomavirus type 16 (HPV16), Tsyn-seq successfully enriched the correct cognate antigen from a cDNA library derived from an HPV16-positive cervical cancer cell line. Tsyn-seq provides a method for rapidly identifying antigens recognized by TCRs of interest from a tumor cDNA library. See related Spotlight by Makani and Joglekar, p. 515.
Keywords
Humans, Antigen-Presenting Cells, Cell Line, Tumor, Gene Library, High-Throughput Nucleotide Sequencing, Human papillomavirus 16, Immunological Synapses, NFATC Transcription Factors, Papillomavirus E7 Proteins, Receptors, Antigen, T-Cell, T-Lymphocytes
DOI
10.1158/2326-6066.CIR-23-0467
PMID
38363296
PMCID
PMC11065584
PubMedCentral® Posted Date
11-2-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons