DeRR: A Unique Detecting Method and the First Landscape for T Cells with Dual T Cell Receptors from Large-scale...

Area of Science:

• Immunology
• Computational Biology
• Genomics

Background:

• Most T cells express a single T cell receptor (TCR), but a subset exhibits dual-TCR expression.
• The functional roles of dual-TCR T cells are known, but their isolation and characterization are challenging.
• Existing methods limit comprehensive analysis of dual-TCR T cells.

Purpose of the Study:

• To develop a computational pipeline, DeRR, for identifying dual-TCR T cells using single-cell sequencing data.
• To provide the first systematic characterization of dual-TCR T cells across diverse samples.
• To explore the prevalence and properties of dual-TCR T cells in different health and disease states.

Main Methods:

• Developed DeRR (Detection of dual T cell Receptors) pipeline.
• Applied DeRR to single-cell TCR and RNA sequencing data (scTCR-seq and scRNA-seq).
• Analyzed over 600,000 single T cells from 147 samples.

Main Results:

• DeRR demonstrated robust performance in identifying dual-TCRs.
• Approximately 17% of T cells had dual TCR α-chains and 12% had dual TCR β-chains.
• Dual-TCR frequency was elevated in cancer and associated with disease duration in autoimmune disorders.
• Dual-TCR T cells showed increased cross-reactivity, especially via secondary TCR chains.
• Dual-TCR T cells were uniformly distributed across subtypes, with dynamic expression levels.

Conclusions:

• DeRR is the first dedicated tool for dual-TCR detection, facilitating T cell immunology research.
• This study provides a comprehensive landscape of dual-TCR T cells, advancing understanding of their role in immunity and disease.
• Dual-TCR T cells exhibit unique properties, including enhanced cross-reactivity and altered prevalence in specific conditions.