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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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A pan-disease and population-level single-cell TCRαβ repertoire reference.

Ziwei Xue1,2, Lize Wu3, Bing Gao1

  • 1Department of Rheumatology and Immunology of the Second Affiliated Hospital, and Centre of Biomedical Systems and Informatics of Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Cell Discovery
|October 14, 2025
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This study built a large T cell receptor (TCR) reference from over 2 million cells, revealing public TCRs linked to common viruses and diseases. A new tool, TCR-DeepInsight, helps identify disease-associated TCR clusters.

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Area of Science:

  • Immunology
  • Genomics
  • Computational Biology

Background:

  • Single-cell technologies now capture T cell receptor (TCR) sequences and gene expression (GEX) simultaneously.
  • Linking TCR repertoire to T cell phenotypes for disease association at a population level is a significant gap.

Purpose of the Study:

  • To construct a large-scale reference of paired single-cell RNA/TCR sequencing (scRNA/TCR-seq) data.
  • To reveal intrinsic features of TCR-major histocompatibility complex (MHC) restriction and identify public TCRs.
  • To develop a computational framework for identifying disease-associated TCR clusters.

Main Methods:

  • Assembled a reference dataset of >2 million T cells from 70 studies, including scRNA/TCR-seq, full-length paired TCR, and HLA genotypes.
  • Analyzed TCR-MHC restriction, public TCR prevalence, clonal expansion, and association with viral epitopes (EBV, CMV, IAV).
  • Developed TCR-DeepInsight, a computational framework for clustering TCRs based on sequence, GEX, and HLA sharing.

Main Results:

  • Revealed germline-encoded TCR-MHC restriction in CD4+/CD8+ T cells.
  • Observed widespread public TCRs associated with high clonal expansion and shared HLA alleles, likely targeting common viral epitopes.
  • Demonstrated TCR-DeepInsight's capability to identify HLA-shared and disease-associated TCR clusters.

Conclusions:

  • The study presents a comprehensive scTCRαβ reference and novel computational methods for TCR analysis.
  • Identified public TCRs associated with viral infections and potential disease links.
  • TCR-DeepInsight facilitates the characterization of functional TCRs and their disease associations.