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Nat Biotechnol. 2016 Oct;34(10):1037-1045. doi: 10.1038/nbt.3662. Epub 2016 Aug 29.

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

Author information

1
Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Copenhagen, Denmark.
2
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
3
Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
4
Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
5
CRUK Lung Cancer Center of Excellence, UCL Cancer Institute, London, UK.
6
Cancer Immunology Unit, UCL Cancer Institute, University College London, London, UK.
7
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK.
8
Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
9
Immudex, Copenhagen, Denmark.

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.

PMID:
27571370
DOI:
10.1038/nbt.3662
[Indexed for MEDLINE]

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