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

    Cite this

    Bentzen, Amalie Kai ; Marquard, Andrea Marion ; Lyngaa, Rikke Birgitte ; Saini, Sunil Kumar ; Andersen, Sofie Ramskov ; Donia, Marco ; Such, Lina ; Furness, Andrew J. S. ; McGranahan, Nicholas ; Rosenthal, Rachel ; Straten, Per Thor ; Szallasi, Zoltan Imre ; Svane, Inge Marie ; Swanton, Charles ; Quezada, Sergio A. ; Jakobsen, Søren Nyboe ; Eklund, Aron Charles ; Hadrup, Sine Reker. / Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes. In: Nature Biotechnology. 2016 ; Vol. 34, No. 10. pp. 1037-1045.
    @article{541f3e4e8bb140e3bb2af579d7a9650d,
    title = "Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes",
    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.",
    author = "Bentzen, {Amalie Kai} and Marquard, {Andrea Marion} and Lyngaa, {Rikke Birgitte} and Saini, {Sunil Kumar} and Andersen, {Sofie Ramskov} and Marco Donia and Lina Such and Furness, {Andrew J. S.} and Nicholas McGranahan and Rachel Rosenthal and Straten, {Per Thor} and Szallasi, {Zoltan Imre} and Svane, {Inge Marie} and Charles Swanton and Quezada, {Sergio A.} and Jakobsen, {S{\o}ren Nyboe} and Eklund, {Aron Charles} and Hadrup, {Sine Reker}",
    year = "2016",
    doi = "10.1038/nbt.3662",
    language = "English",
    volume = "34",
    pages = "1037--1045",
    journal = "Nature Biotechnology",
    issn = "1087-0156",
    publisher = "Nature Publishing Group",
    number = "10",

    }

    Bentzen, AK, Marquard, AM, Lyngaa, RB, Saini, SK, Andersen, SR, Donia, M, Such, L, Furness, AJS, McGranahan, N, Rosenthal, R, Straten, PT, Szallasi, ZI, Svane, IM, Swanton, C, Quezada, SA, Jakobsen, SN, Eklund, AC & Hadrup, SR 2016, 'Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes', Nature Biotechnology, vol. 34, no. 10, pp. 1037-1045. https://doi.org/10.1038/nbt.3662

    Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes. / Bentzen, Amalie Kai; Marquard, Andrea Marion; Lyngaa, Rikke Birgitte; Saini, Sunil Kumar; Andersen, Sofie Ramskov; Donia, Marco; Such, Lina; Furness, Andrew J. S.; McGranahan, Nicholas; Rosenthal, Rachel; Straten, Per Thor; Szallasi, Zoltan Imre; Svane, Inge Marie; Swanton, Charles; Quezada, Sergio A.; Jakobsen, Søren Nyboe; Eklund, Aron Charles; Hadrup, Sine Reker.

    In: Nature Biotechnology, Vol. 34, No. 10, 2016, p. 1037-1045.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes

    AU - Bentzen, Amalie Kai

    AU - Marquard, Andrea Marion

    AU - Lyngaa, Rikke Birgitte

    AU - Saini, Sunil Kumar

    AU - Andersen, Sofie Ramskov

    AU - Donia, Marco

    AU - Such, Lina

    AU - Furness, Andrew J. S.

    AU - McGranahan, Nicholas

    AU - Rosenthal, Rachel

    AU - Straten, Per Thor

    AU - Szallasi, Zoltan Imre

    AU - Svane, Inge Marie

    AU - Swanton, Charles

    AU - Quezada, Sergio A.

    AU - Jakobsen, Søren Nyboe

    AU - Eklund, Aron Charles

    AU - Hadrup, Sine Reker

    PY - 2016

    Y1 - 2016

    N2 - 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.

    AB - 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.

    U2 - 10.1038/nbt.3662

    DO - 10.1038/nbt.3662

    M3 - Journal article

    C2 - 27571370

    VL - 34

    SP - 1037

    EP - 1045

    JO - Nature Biotechnology

    JF - Nature Biotechnology

    SN - 1087-0156

    IS - 10

    ER -