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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
Published on: January 12, 2021
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Mapping the functional landscape of T cell receptor repertoires by single-T cell transcriptomics
Ze Zhang1, Danyi Xiong2, Xinlei Wang2
1Quantitative Biomedical Research Center, Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature Methods
|January 7, 2021
Summary
Tessa, a new tool, links T cell receptors (TCRs) to T cell function. It reveals how TCR similarity shapes T cell phenotypes and antigen targeting, impacting immunotherapy and tumor biology.
Area of Science:
- Immunology
- Bioinformatics
- Computational Biology
Background:
- Characterizing the human T cell receptor (TCR) repertoire is crucial for understanding T cell biology.
- The functional relevance of TCR profiling remains largely unknown, hindering unbiased interpretation.
- Existing bioinformatics approaches often lack integration with functional T cell phenotypes.
Purpose of the Study:
- To develop a computational tool, tessa, for integrating TCR sequences with T cell gene expression.
- To estimate the functional impact of TCRs on T cell phenotypes.
- To provide a method for unbiased interpretation of T cell biology and TCR repertoire data.
Main Methods:
- Leveraged single-cell RNA-sequencing (scRNA-seq) combined with TCR sequencing.
- Developed the tessa tool to integrate TCR data with single-cell gene expression profiles.
- Validated tessa against existing TCR sequencing-only approaches.
Main Results:
- Tessa demonstrated superior performance compared to methods analyzing only TCR sequences.
- TCR similarity was shown to constrain T cell phenotypes towards similarity.
- A gradient in antigen targeting efficiency was observed for T cell clonotypes with convergent TCRs.
- TCR constraints could predict functional dichotomization of T cells after immunotherapy.
- This TCR-mediated constraint was found to be weakened in tumor contexts.
Conclusions:
- Tessa provides a novel approach to link TCR sequences with T cell function and phenotype.
- TCR repertoire analysis, when integrated with gene expression, offers deeper biological insights.
- The findings highlight the role of TCRs in shaping T cell responses in immunotherapy and cancer.
