Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes
Authors listAmalie Kai Bentzen Andrea Marion Marquard Rikke Lyngaa Sunil Kumar Saini Sofie Ramskov Marco Donia Lina Such Andrew JS Furness Nicholas McGranahan Rachel Rosenthal Per thor Straten Zoltan Szallasi Inge Marie Svane Charles Swanton Sergio A Quezada Søren Nyboe Jakobsen Aron Charles Eklund Sine Reker Hadrup
Identification of the peptides recognized by individual T cells is important for understanding and treating immune-related diseases. Current cytometry-based approaches are limited to the simultaneous screening of 10-100 distinct T-cell specificities in one sample. Here we use peptide-major histocompatibility complex (MHC) multimers labeled with individual DNA barcodes to screen >1,000 peptide specificities in a single sample, and detect low-frequency CD8 T cells specific for virus- or cancer-restricted antigens. When analyzing T-cell recognition of shared melanoma antigens before and after adoptive cell therapy in melanoma patients, we observe a greater number of melanoma-specific T-cell populations compared with cytometry-based approaches. Furthermore, we detect neoepitope-specific T cells in tumor-infiltrating lymphocytes and peripheral blood from patients with non-small cell lung cancer. Barcode-labeled pMHC multimers enable the combination of functional T-cell analysis with large-scale epitope recognition profiling for the characterization of T-cell recognition in various diseases, including in small clinical samples.
Journal Nature Biotechnology
Issue number 10