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