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; Eivind Per thor Straten; Zoltan Szallasi; Inge Marie Svane; Charles Swanton; Sergio A. Quezada; Søren Nyboe Jakobsen; Aron Charles Eklund; Sine Reker Hadrup

doi:10.1038/nbt.3662

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, Eivind Per thor Straten, Zoltan Szallasi, Inge Marie Svane, Charles Swanton, Sergio A. Quezada, Søren Nyboe Jakobsen, Aron Charles Eklund, Sine Reker Hadrup^*

^*Corresponding author for this work

Department of Clinical Medicine

130 Citations (Scopus)

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 language	English
Journal	Nature Biotechnology
Volume	34
Issue number	10
Pages (from-to)	1037-1045
Number of pages	9
ISSN	1087-0156
DOIs	https://doi.org/10.1038/nbt.3662
Publication status	Published - Oct 2016

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Bentzen, A. K., Marquard, A. M., Lyngaa, R., Saini, S. K., Ramskov, S., Donia, M., Such, L., Furness, A. J. S., McGranahan, N., Rosenthal, R., thor Straten, E. P., Szallasi, Z., Svane, I. M., Swanton, C., Quezada, S. A., Jakobsen, S. N., Eklund, A. C., & Hadrup, S. R. (2016). Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes. Nature Biotechnology, 34(10), 1037-1045. https://doi.org/10.1038/nbt.3662

Bentzen, AK, Marquard, AM, Lyngaa, R, Saini, SK, Ramskov, S, Donia, M, Such, L, Furness, AJS, McGranahan, N, Rosenthal, R, thor Straten, EP, Szallasi, Z, 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

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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.",

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AU - Bentzen, Amalie Kai

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AU - Saini, Sunil Kumar

AU - Ramskov, Sofie

AU - Donia, Marco

AU - Such, Lina

AU - Furness, Andrew J S

AU - McGranahan, Nicholas

AU - Rosenthal, Rachel

AU - thor Straten, Eivind Per

AU - Szallasi, Zoltan

AU - Svane, Inge Marie

AU - Swanton, Charles

AU - Quezada, Sergio A.

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AU - Eklund, Aron Charles

AU - Hadrup, Sine Reker

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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.

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

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