# Development of an emulsion-based method for repertoire-scale paired-chain T cell receptor sequencing

> **NIH NIH R21** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $225,868

## Abstract

Project Abstract
T cell recognition of peptide-Major Histocompatibility Complexes is a key determinant of response to infection,
cancer, and autoimmunity. While there have been recent technological advances that have enabled better
tracking and analysis of the T cell receptor repertoire, these approaches are extremely resource intensive and/or
have key technical limitations. Here, we propose a novel method that combines emulsion-based partitioning and
computational sequence deconvolution to enable large-scale determination of the naive T cell repertoire at
modest cost (estimated to be ~$1/3,000 cells at current reagent and sequencing costs, as compared to the
~$1/cell for current techniques). We will first develop and validate the experimental modifications to establish
this technique, including development of low-cost DNA barcoding beads, formation of cell/bead emulsions, and
efficient conversion and capture of TCR transcripts. We will then extend our previous computational approach
to deconvolute pools of TCRα/TCRβ sequences, and validate our method on T cells obtained from healthy
donors. In addition, we will extend our methodology to include oligonucleotide tagged pMHC multimers, enabling
repertoire-scale tracking of TCRα/TCRβ-pMHC pairings. Together, these technologies will enable efforts to track
the T cell repertoire at extremely large scale, an advance necessary for both mechanistic immunology and
computational prediction of antigen reactivity.

## Key facts

- **NIH application ID:** 10110234
- **Project number:** 1R21AI156664-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Michael Birnbaum
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,868
- **Award type:** 1
- **Project period:** 2021-03-12 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110234

## Citation

> US National Institutes of Health, RePORTER application 10110234, Development of an emulsion-based method for repertoire-scale paired-chain T cell receptor sequencing (1R21AI156664-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10110234. Licensed CC0.

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