Journal
NATURE IMMUNOLOGY
Volume 21, Issue 10, Pages 1232-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-0770-x
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Funding
- Kennedy Trust for Rheumatology (KTRR) Prize Studentship
- UCB-Oxford Post-doctoral Fellowship
- Research Council of Norway
- Marie Sklodowska-Curie Actions [275466]
- Wellcome Trust Principal Research Fellowship [100262Z/12/Z]
- KTRR
- Kennedy Institute Microscopy Facility
- Weatherall Institute Microscopy Facility
- Human Frontiers Science Program
- German Research Foundation (DFG)
- Collaborative Research Center 'Molecular Organization of Cellular Communication within the Immune System' [SFB 854]
- Philippe Foundation
- Wellcome Trust Senior Research Fellowship [207537/Z/17/Z]
- Oxford Gastro-Intestinal Biobank
- Oxford Inflammatory Bowel Disease Cohort
- NIHR Oxford Biomedical Research Centre
- MRC [MC_PC_MR/S025952/1, MR/S036377/1, MC_UU_00008/7, MC_UU_12010/7] Funding Source: UKRI
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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-gamma 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.
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