Identification and tracking of alloreactive T cell clones in Rhesus Macaques through the RM-scTCR-Seq platform

  • Biology
  • Cell Atlas
  • Computational Methods
  • Genomics
  • Immunology
  • R&D
  • Technology
  • Jim Kaminski
  • Alex K. Shalek
  • Gerdemann et al.▾
    Gerdemann, U.*, Fleming, R.A.*, Kaminski, J., McGuckin, C., Rui, X., Lane, J.F., Keskula, P., Cagnin, L., Shalek, A.K.#, Tkachev, V.#, Kean, L.S.#
  • Frontiers in Immunology , Volume 12
  • February, 2023
Biology
Cell Atlas
Computational Methods
Genomics
Immunology
R&D
Technology
Jim Kaminski
Alex K. Shalek

Abstract

T cell receptor (TCR) clonotype tracking is a powerful tool for interrogating T cell mediated immune processes. New methods to pair a single cell’s transcriptional program with its TCR identity allow monitoring of T cell clonotype-specific transcriptional dynamics. While these technologies have been available for human and mouse T cells studies, they have not been developed for Rhesus Macaques (RM), a critical translational organism for autoimmune diseases, vaccine development and transplantation. We describe a new pipeline, ‘RM-scTCR-Seq’, which, for the first time, enables RM specific single cell TCR amplification, reconstruction and pairing of RM TCR’s with their transcriptional profiles. We apply this method to a RM model of GVHD, and identify and track in vitro detected alloreactive clonotypes in GVHD target organs and explore their GVHD driven cytotoxic T cell signature. This novel, state-of-the-art platform fundamentally advances the utility of RM to study protective and pathogenic T cell responses.

Identification and tracking of alloreactive T cell clones in Rhesus Macaques through the RM-scTCR-Seq platform