Abstract
T cells bearing γδ T cell antigen receptors (TCRs) function in lymphoid stress surveillance. However, the contribution of γδ TCRs to such responses is unclear. Here we found that the TCR of a human V(γ)4V(δ)5 clone directly bound endothelial protein C receptor (EPCR), which allowed γδ 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(γ)4V(δ)5 TCR bound EPCR independently of lipids, in an antibody-like way. Moreover, the recognition of target cells by γδ T cells required a multimolecular stress signature composed of EPCR and costimulatory ligand(s). Our results demonstrate how a γδ TCR mediates recognition of broadly stressed human cells by engaging a stress-regulated self antigen.
MeSH terms
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Antigens, CD / immunology*
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Antigens, CD / metabolism
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Cytomegalovirus / immunology
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Cytomegalovirus Infections / immunology*
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Endothelial Protein C Receptor
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Humans
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Immunoblotting
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Immunologic Surveillance / immunology*
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Immunoprecipitation
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Neoplasms, Glandular and Epithelial / immunology*
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Protein Binding
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Receptors, Antigen, T-Cell, gamma-delta / chemistry
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Receptors, Antigen, T-Cell, gamma-delta / immunology*
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Receptors, Antigen, T-Cell, gamma-delta / metabolism
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Receptors, Cell Surface / immunology*
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Receptors, Cell Surface / metabolism
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Stress, Physiological / immunology*
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T-Lymphocyte Subsets / chemistry
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes / chemistry
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Antigens, CD
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Endothelial Protein C Receptor
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PROCR protein, human
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Cell Surface