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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

582
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...
582

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Defining T cell receptor repertoires using nanovial-based binding and functional screening.

Doyeon Koo1, Zhiyuan Mao2, Robert Dimatteo3

  • 1Department of Bioengineering, University of California, Los Angeles, CA 90095.

Proceedings of the National Academy of Sciences of the United States of America
|March 27, 2024
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Summary

Researchers developed nanovials to isolate and sequence T cell receptors (TCRs) for immunotherapy. This method identifies functional TCRs targeting viral and cancer antigens, advancing T cell therapy development.

Keywords:
TCR immunotherapyTCR sequencingsingle-cell secretion analysis

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Area of Science:

  • Immunology
  • Biotechnology
  • Molecular Biology

Background:

  • T cell receptor (TCR) immunotherapies rely on identifying rare T cells with therapeutic potential.
  • Isolating antigen-reactive T cells based on both binding affinity and effector function is challenging.

Purpose of the Study:

  • To develop a novel method for isolating and characterizing antigen-reactive T cells.
  • To identify and rank T cell receptors (TCRs) with therapeutic potential against viral and cancer antigens.

Main Methods:

  • Utilized peptide-major histocompatibility complex (pMHC) coated nanovials to capture and activate T cells.
  • Collected and sequenced T cell receptors (TCRs) from sorted cells using microfluidic emulsion-based single-cell sequencing.
  • Employed oligonucleotide-barcoded nanovials and detection antibodies to link TCR sequences to specific targets and functional output.

Main Results:

  • Successfully isolated antigen-reactive T cells based on pMHC binding and effector molecule secretion (IFN-γ, granzyme B).
  • Identified a broad range of functional TCRs targeting viral antigens with high specificity.
  • Discovered rare TCRs exhibiting activity against cancer-specific splicing-enhanced epitopes.

Conclusions:

  • Nanovial technology enables efficient isolation and functional characterization of T cells for TCR discovery.
  • This approach significantly advances the identification of TCRs for next-generation immunotherapies.
  • The method allows for the ranking of TCRs based on their functional potency against specific targets.