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

Ioannis D. Dimitriou, Korris Lee, Itoro Akpan, Evan Lind, Valarie A. Barr, Pamela S. Ohashi, Lawrence E. Samelson, Robert Rottapel

Research output: Contribution to journalArticle

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. Dimitriou et al. show that the adaptor protein 3BP2 lowers the threshold of T cell activation and that the induction of the 3BP2 signaling module at later time points may serve to recapitulate and prolong the biochemical signals emanating from the TCR required for sustained MHC:peptide-independent T cell proliferation.

Original languageEnglish (US)
Pages (from-to)1123-1135
Number of pages13
JournalCell Reports
Volume24
Issue number5
DOIs
StatePublished - Jul 31 2018

Fingerprint

T-cells
Cell Differentiation
T-Lymphocytes
Chemical activation
Cell proliferation
Cell Proliferation
Peptide T
Data storage equipment
Peptides
Antigen-Presenting Cells
Cell Communication
Immunity
Cells
Molecules
Sensors
Population
Proteins

Keywords

  • 3BP2
  • CD8 T cells
  • differentiation
  • microclusters
  • proliferation
  • TCR signaling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dimitriou, I. D., Lee, K., Akpan, I., Lind, E., Barr, V. A., Ohashi, P. S., ... Rottapel, R. (2018). Timed Regulation of 3BP2 Induction Is Critical for Sustaining CD8+ T Cell Expansion and Differentiation. Cell Reports, 24(5), 1123-1135. https://doi.org/10.1016/j.celrep.2018.06.075

Timed Regulation of 3BP2 Induction Is Critical for Sustaining CD8+ T Cell Expansion and Differentiation. / Dimitriou, Ioannis D.; Lee, Korris; Akpan, Itoro; Lind, Evan; Barr, Valarie A.; Ohashi, Pamela S.; Samelson, Lawrence E.; Rottapel, Robert.

In: Cell Reports, Vol. 24, No. 5, 31.07.2018, p. 1123-1135.

Research output: Contribution to journalArticle

Dimitriou, ID, Lee, K, Akpan, I, Lind, E, Barr, VA, Ohashi, PS, Samelson, LE & Rottapel, R 2018, 'Timed Regulation of 3BP2 Induction Is Critical for Sustaining CD8+ T Cell Expansion and Differentiation', Cell Reports, vol. 24, no. 5, pp. 1123-1135. https://doi.org/10.1016/j.celrep.2018.06.075
Dimitriou, Ioannis D. ; Lee, Korris ; Akpan, Itoro ; Lind, Evan ; Barr, Valarie A. ; Ohashi, Pamela S. ; Samelson, Lawrence E. ; Rottapel, Robert. / Timed Regulation of 3BP2 Induction Is Critical for Sustaining CD8+ T Cell Expansion and Differentiation. In: Cell Reports. 2018 ; Vol. 24, No. 5. pp. 1123-1135.
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