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T cell antigen discovery

Nature Methods volume 18, pages 873–880 (2021)Cite this article

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Abstract

T cells respond to threats in an antigen-specific manner using T cell receptors (TCRs) that recognize short peptide antigens presented on major histocompatibility complex (MHC) proteins. The TCR–peptide-MHC interaction mediated between a T cell and its target cell dictates its function and thereby influences its role in disease. A lack of approaches for antigen discovery has limited the fundamental understanding of the antigenic landscape of the overall T cell response. Recent advances in high-throughput sequencing, mass cytometry, microfluidics and computational biology have led to a surge in approaches to address the challenge of T cell antigen discovery. Here, we summarize the scope of this challenge, discuss in depth the recent exciting work and highlight the outstanding questions and remaining technical hurdles in this field.

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Fig. 1: Molecular basis of TCR–pMHC recognition.
Fig. 2: Schematic antigen-directed methods.
Fig. 3: Schematic TCR-directed methods.
Fig. 4: Comparison of antigen-discovery methods.

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Acknowledgements

We thank K. Ford and K. Rankin for comments and suggestions on the manuscript. The figures were created with BioRender.com. This work was supported by the National Natural Science Foundation (81972875), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2019PT310028) and The CAMS Initiative for Innovative Medicine (2016-I2M-1-005).

Author information

Authors and Affiliations

  1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Alok V. Joglekar

  2. Center for Systems Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Alok V. Joglekar

  3. Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Alok V. Joglekar

  4. Center of Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Guideng Li

  5. Suzhou Institute of Systems Medicine, Suzhou, China

    Guideng Li

  6. Key Laboratory of Synthetic Biology Regulatory Element, Chinese Academy of Medical Sciences, Beijing, China

    Guideng Li

Authors
  1. Alok V. Joglekar
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  2. Guideng Li
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Correspondence to Alok V. Joglekar or Guideng Li.

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Joglekar, A.V., Li, G. T cell antigen discovery. Nat Methods 18, 873–880 (2021). https://doi.org/10.1038/s41592-020-0867-z

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