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Issue 18, 2019
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MATE-Seq: microfluidic antigen-TCR engagement sequencing

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Abstract

Adaptive immunity is based on peptide antigen recognition. Our ability to harness the immune system for therapeutic gain relies on the discovery of the T cell receptor (TCR) genes that selectively target antigens from infections, mutated proteins, and foreign agents. Here we present a method that selectively labels peptide antigen-specific CD8+ T cells using magnetic nanoparticles functionalized with peptide–MHC tetramers, isolates these specific cells within an integrated microfluidic device, and directly amplifies the TCR genes for sequencing. Critically, the identity of the peptide recognized by the TCR is preserved, providing the link between peptide and gene. The platform requires inputs on the order of just 100 000 CD8+ T cells, can be multiplexed for simultaneous analysis of multiple peptides, and performs sorting and isolation on chip. We demonstrate 1000-fold sensitivity enhancement of detecting antigen-specific TCRs relative to bulk analysis and simultaneous capture of two virus antigen-specific TCRs from a population of T cells.

Graphical abstract: MATE-Seq: microfluidic antigen-TCR engagement sequencing

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Supplementary files

Article information


Submitted
06 Jun 2019
Accepted
05 Aug 2019
First published
08 Aug 2019

Lab Chip, 2019,19, 3011-3021
Article type
Paper

MATE-Seq: microfluidic antigen-TCR engagement sequencing

A. H. C. Ng, S. Peng, A. M. Xu, W. J. Noh, K. Guo, M. T. Bethune, W. Chour, J. Choi, S. Yang, D. Baltimore and J. R. Heath, Lab Chip, 2019, 19, 3011
DOI: 10.1039/C9LC00538B

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