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.
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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.
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