Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes
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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; Saini, Sunil Kumar; Ramskov, Sofie; Donia, Marco; Such, Lina; Furness, Andrew J S; McGranahan, Nicholas; Rosenthal, Rachel; thor Straten, Eivind Per; Szallasi, Zoltan; Svane, Inge Marie; Swanton, Charles; Quezada, Sergio A.; Jakobsen, Søren Nyboe; Eklund, Aron Charles; Hadrup, Sine Reker.
I: Nature Biotechnology, Bind 34, Nr. 10, 10.2016, s. 1037-1045.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
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.
AU - Jakobsen, Søren Nyboe
AU - Eklund, Aron Charles
AU - Hadrup, Sine Reker
PY - 2016/10
Y1 - 2016/10
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
AN - SCOPUS:84992109841
VL - 34
SP - 1037
EP - 1045
JO - Nature Biotechnology
JF - Nature Biotechnology
SN - 1087-0156
IS - 10
ER -
ID: 169080275