Journal
NATURE BIOTECHNOLOGY
Volume 34, Issue 10, Pages 1037-1045Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.3662
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Funding
- Danish Cancer Society [ID:R72-A4531-13-S2]
- Lundbeck Foundation Fellowship [R190-2014-4178]
- Danish Research Council (FSS) [1331-00283]
- Danish Research Council (DFF) [4004-00422]
- Familien Erichsens Mindefond
- Cancer Research UK [FC001169]
- UK Medical Research Council [FC001169, MR/FC001169/1]
- Wellcome Trust [FC001169]
- Novo Nordisk Foundation [16584]
- Cancer Research UK [20466, 12100] Funding Source: researchfish
- Lundbeck Foundation [R181-2014-3828] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0016584] Funding Source: researchfish
- The Danish Cancer Society [R72-A4531] Funding Source: researchfish
- Versus Arthritis
- Cancer Research UK [20265] Funding Source: researchfish
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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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