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

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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Bentzen AK,Marquard AM,Lyngaa R,Saini SK,Ramskov S,Donia M,Such L,Furness AJ,McGranahan N,Rosenthal R,Straten PT,Szallasi Z,Svane IM,Swanton C,Quezada SA,Jakobsen SN,Eklund AC,Hadrup SR

doi

10.1038/nbt.3662

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

1037-1045

issue

10

eissn

1087-0156

issn

1546-1696

pii

nbt.3662

journal_volume

34

pub_type

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