1. A dynamic CD2-rich compartment at the outer edge of the immunological synapse boosts and integrates signals
- Author
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Mikhail A Kutuzov, H Rada, Matteo Morotti, Ahmed Ashour Ahmed, A Kvalvaag, S Yusuf, Nina Wietek, Jehan Afrose, David Depoil, Salvatore Valvo, Enas Abu-Shah, Michael Meyer-Hermann, Matthias Friedrich, Thomas Starkey, Viveka Mayya, Lee Lyw., Michael L. Dustin, Elizabeth R. Mann, Philippos Demetriou, Kseniya Korobchevskaya, Anastasios Siokis, and Sarah McCuaig
- Subjects
0301 basic medicine ,Immunological Synapses ,CD58 ,T cell ,Immunology ,Programmed Cell Death 1 Receptor ,CD2 Antigens ,Receptors, Antigen, T-Cell ,Biology ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Article ,Immunological synapse ,03 medical and health sciences ,0302 clinical medicine ,Lymphocytes, Tumor-Infiltrating ,Neoplasms ,medicine ,Cell Adhesion ,Immune Tolerance ,Immunology and Allergy ,Humans ,Cell adhesion ,Cells, Cultured ,T-cell receptor ,CD28 ,Receptor Cross-Talk ,CD58 Antigens ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Signal transduction ,Single-Cell Analysis ,CD8 ,030215 immunology ,Protein Binding ,Signal Transduction - 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. The adhesion receptor CD2 plays an important role in the full activation of T cells. Dustin and colleagues show that CD2 occupies a region in the periphery of the immunological synapse where it amplifies cognate antigen signals, whereas the presence of PD-1 disrupts this effect.
- Published
- 2019