Nicola Ferrari, Biomarker and Experimental Medicine Leader at Roche, shared on LinkedIn:
“The challenge and promise of studying human antigen-specific T cells
- This Review describes the technologies and computational approaches that are helping to link T cell receptor specificity with function, revealing how intrinsic T cell properties shape immune outcomes across infection, vaccination and disease.
- Antigen-specific T cells remain difficult to study as each antigen-specific T cell population represents only a small fraction of the total T cell repertoire (<1% of circulating T cells).
- Several methods are available for the identification and isolation of antigen-specific T cells. These include approaches based on TCR binding, such as pMHC tetramers and dextramers, as well as methods that isolate cells based on their response to stimulation, including activation-induced marker assays and cytokine secretion assays. However, each of these methods has advantages and limitations.
- The emergence of large single-cell RNA sequencing datasets has enabled the investigation of T cells at an unprecedented level of resolution. When combined with high-quality antigen-specific T cell datasets, with defined epitope specificity and HLA restriction, these approaches allow detailed characterization of the phenotype and functional properties of antigen-specific T cells.
- Studies of antigen-specific T cells are revealing fundamental aspects of T cell immunology often hidden in bulk populations. Consequently, analysing antigen-specific subsets frequently challenges or contradicts conclusions drawn from unselected bulk T cell analyses.
- As knowledge of antigen-specific T cells and their roles in disease pathogenesis continues to expand, new therapeutic opportunities are likely to emerge. These include strategies harnessing antigen-specific T cells in cancer and viral infection or targeting them in autoimmune disease, as well as using antigen-specific T cells themselves as therapeutic agents.”
Title: The challenge and promise of studying human antigen-specific T cells
Authors: Sam Farrar, Elie Antoun, Julian C. Knight, Yanchun Peng, Tao Dong
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