Journal article
Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes
National Veterinary Institute, Technical University of Denmark1
Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark2
Department of Systems Biology, Technical University of Denmark3
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark4
Cancer Systems Biology, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark5
University of Copenhagen6
University College London7
The Francis Crick Institute8
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.
Language: | English |
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Publisher: | Nature Publishing Group US |
Year: | 2016 |
Pages: | 1037-1045 |
Journal subtitle: | Science and Business of Biotechnology |
ISSN: | 15461696 and 10870156 |
Types: | Journal article |
DOI: | 10.1038/nbt.3662 |
ORCIDs: | 0000-0003-2928-6017 , Saini, Sunil Kumar , Eklund, Aron Charles , Hadrup, Sine Reker , 0000-0002-4731-4969 , 0000-0002-9451-6037 , Bentzen, Amalie Kai and Andersen, Sofie Ramskov |