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

Bentzen, AK; Marquard, AM; Lyngaa, R; Saini, SK; Ramskov, S; Donia, M; Such, L; ... Hadrup, SR; + view all (2016) Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes. Nature Biotechnology , 34 (10) pp. 1037-1045. 10.1038/nbt.3662. Green open access

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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.

Type: Article
Title: Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nbt.3662
Publisher version: http://doi.org/10.1038/nbt.3662
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/10051958
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