New St. Jude Technique Dramatically Lowers Cost of T-Cell Receptor Analysis

A team at St. Jude Children’s Research Hospital has developed a groundbreaking technique to make T-cell receptor (TCR) analysis far more accessible and affordable. Their method, called Throughput-Intensive Rapid TCR Library sequencing (TIRTL-seq), captures a far more complete picture of a person’s T-cell repertoire — and at roughly 10% of the cost of traditional methods.

Why This Matters

T cells are central to our immune defense, but analyzing their receptors is typically expensive and labor-intensive. Traditional approaches often process only tens of thousands of cells: for example, assays that handle 20,000 cells cost around $2,000 and must be run multiple times.
TIRTL-seq revolutionizes this by enabling the analysis of tens of millions of T cells in a single run — the St. Jude team demonstrated processing up to 30 million T cells at once.
This scale dramatically reduces cost: TIRTL-seq can analyze 10 million cells for about $200.

How the Method Works

TIRTL-seq combines automation, optimized lab protocols, and streamlined computational workflows. By dividing a full sample into many subsamples, the technique leverages statistical methods that improve sequencing accuracy and pairing of the two halves of the T-cell receptor.
This clever combination allows far more cells to be sequenced, with reliable pairing, without driving up costs.

Demonstrated Use Case

To show what TIRTL-seq makes possible, researchers used it to analyze blood samples from the SJTRC (St. Jude Tracking Study of Immune Responses Associated with COVID-19).
They tracked how a person’s T-cell repertoire shifted before and after SARS-CoV-2 infection, and they even detected a previously unnoticed Epstein-Barr virus infection
These results highlight how deeply TIRTL-seq can profile immune memory — and suggest potential future applications, such as diagnostics.

Accessibility & Impact

Importantly, St. Jude has made the full TIRTL-seq protocol publicly available, complete with step-by-step instructions.
According to Victor Torres, PhD, chair of the Department of Host-Microbe Interactions at St. Jude, this democratization of TCR analysis could unlock new discoveries:

“TIRTL-seq can perform a highly detailed analysis of many T-cell receptors … at a cost that makes these experiments feasible for more scientists than ever before.”

Future Directions

The St. Jude team plans to use TIRTL-seq to deepen understanding of how immune memory develops, how it responds to infections, and how it might be harnessed in treatments for cancer or other diseases.
Because the method is highly scalable and cost-effective, it could accelerate research across labs previously limited by budget or technical constraints.

Study Details