Universal antigen encoding of T cell activation from high-dimensional cytokine dynamics

Science. 2022 May 20;376(6595):880-884. doi: 10.1126/science.abl5311. Epub 2022 May 19.

Abstract

Systems immunology lacks a framework with which to derive theoretical understanding from high-dimensional datasets. We combined a robotic platform with machine learning to experimentally measure and theoretically model CD8+ T cell activation. High-dimensional cytokine dynamics could be compressed onto a low-dimensional latent space in an antigen-specific manner (so-called "antigen encoding"). We used antigen encoding to model and reconstruct patterns of T cell immune activation. The model delineated six classes of antigens eliciting distinct T cell responses. We generalized antigen encoding to multiple immune settings, including drug perturbations and activation of chimeric antigen receptor T cells. Such universal antigen encoding for T cell activation may enable further modeling of immune responses and their rational manipulation to optimize immunotherapies.

MeSH terms

  • Antigens* / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Cytokines*
  • Humans
  • Immunotherapy
  • Lymphocyte Activation*
  • Machine Learning
  • Models, Immunological*
  • Receptors, Antigen, T-Cell / metabolism

Substances

  • Antigens
  • Cytokines
  • Receptors, Antigen, T-Cell