Journal
NATURE IMMUNOLOGY
Volume 13, Issue 9, Pages 872-879Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2394
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Funding
- Fondation pour la Recherche Medicate [DEQ20051205738, DEQ20110421287]
- Agence Nationale de la Recherche [ANR-05-JCJC-0129-01]
- Ligue Nationale contre le Cancer
- Association pour la Recherche sur le Cancer [A09-1-5022]
- Institut National contre le Cancer Cancer Research UK [C17422-A7986, C17422-A11740]
- Wellcome Trust
- Boehringer Ingelheim Fonds
- Cancer Research UK [19309] Funding Source: researchfish
- Medical Research Council [G9818340B, MR/J006742/1, G0600698B] Funding Source: researchfish
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T cells bearing gamma delta T cell antigen receptors (TCRs) function in lymphoid stress surveillance. However, the contribution of gamma delta TCRs to such responses is unclear. Here we found that the TCR of a human V(gamma)4V(delta)5 clone directly bound endothelial protein C receptor (EPCR), which allowed gamma delta T cells to recognize both endothelial cells targeted by cytomegalovirus and epithelial tumors. EPCR is a major histocompatibility complex-like molecule that binds lipids analogously to the antigen-presenting molecule CD1d. However, the V(gamma)4V(delta)5 TCR bound EPCR independently of lipids, in an antibody-like way. Moreover, the recognition of target cells by gamma delta T cells required a multimolecular stress signature composed of EPCR and costimulatory ligand(s). Our results demonstrate how a gamma delta TCR mediates recognition of broadly stressed human cells by engaging a stress-regulated self antigen.
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