Timed Regulation of 3BP2 Induction Is Critical for Sustaining CD8+ T Cell Expansion and Differentiation

Cell Rep. 2018 Jul 31;24(5):1123-1135. doi: 10.1016/j.celrep.2018.06.075.

Abstract

Successful anti-viral response requires the sustained activation and expansion of CD8+ T cells for periods that far exceed the time limit of physical T cell interaction with antigen-presenting cells (APCs). The expanding CD8+ T cell pool generates the effector and memory cell populations that provide viral clearance and long-term immunity, respectively. Here, we demonstrate that 3BP2 is recruited in cytoplasmic microclusters and nucleates a signaling complex that facilitates MHC:peptide-independent activation of signaling pathways downstream of the TCR. We show that induction of the adaptor molecule 3BP2 is a sensor of TCR signal strength and is critical for sustaining CD8+ T cell proliferation and regulating effector and memory differentiation.

Keywords: 3BP2; CD8(+) T cells; TCR signaling; differentiation; microclusters; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Proliferation*
  • Cells, Cultured
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • Receptors, Antigen, T-Cell
  • Sh3bp2 protein, mouse