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

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

SN - 1087-0156

VL - 34

SP - 1037

EP - 1045

JO - Nature Biotechnology

JF - Nature Biotechnology

IS - 10

ER -