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

Amalie Kai Bentzen, Andrea Marion Marquard, Rikke Birgitte Lyngaa, Sunil Kumar Saini, Sofie Ramskov Andersen, Marco Donia, Lina Such, Andrew J. S. Furness, Nicholas McGranahan, Rachel Rosenthal, Per Thor Straten, Zoltan Imre Szallasi, Inge Marie Svane, Charles Swanton, Sergio A. Quezada, Søren Nyboe Jakobsen, Aron Charles Eklund, Sine Reker Hadrup

    Research output: Contribution to journalJournal articleResearchpeer-review

    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.
    Original languageEnglish
    JournalNature Biotechnology
    Volume34
    Issue number10
    Pages (from-to)1037-1045
    ISSN1087-0156
    DOIs
    Publication statusPublished - 2016

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