A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals

Nat Immunol. 2020 Oct;21(10):1232-1243. doi: 10.1038/s41590-020-0770-x. Epub 2020 Sep 14.

Abstract

The CD2-CD58 recognition system promotes adhesion and signaling and counters exhaustion in human T cells. We found that CD2 localized to the outer edge of the mature immunological synapse, with cellular or artificial APC, in a pattern we refer to as a 'CD2 corolla'. The corolla captured engaged CD28, ICOS, CD226 and SLAM-F1 co-stimulators. The corolla amplified active phosphorylated Src-family kinases (pSFK), LAT and PLC-γ over T cell receptor (TCR) alone. CD2-CD58 interactions in the corolla boosted signaling by 77% as compared with central CD2-CD58 interactions. Engaged PD-1 invaded the CD2 corolla and buffered CD2-mediated amplification of TCR signaling. CD2 numbers and motifs in its cytoplasmic tail controlled corolla formation. CD8+ tumor-infiltrating lymphocytes displayed low expression of CD2 in the majority of people with colorectal, endometrial or ovarian cancer. CD2 downregulation may attenuate antitumor T cell responses, with implications for checkpoint immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD2 Antigens / metabolism*
  • CD58 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Adhesion
  • Cells, Cultured
  • Humans
  • Immune Tolerance
  • Immunological Synapses / metabolism*
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Neoplasms / metabolism*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Protein Binding
  • Receptor Cross-Talk
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • Single-Cell Analysis

Substances

  • CD2 Antigens
  • CD58 Antigens
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell