Please cite

Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes

Amalie Kai Bentzen, Andrea Marion Marquard, Rikke Lyngaa, Sunil Kumar Saini, Sofie Ramskov, Marco Donia, Lina Such, Andrew J S 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

https://www.ncbi.nlm.nih.gov/pubmed/27571370

Abstract

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.