| Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. | |
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MedLine Citation:
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PMID: 17291279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human Vgamma2Vdelta2 T cells play important roles in mediating immunity against microbial pathogens and have potent anti-tumor activity. Vgamma2Vdelta2 T cells recognize the pyrophosphorylated isoprenoid intermediates (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), an intermediate in the foreign 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, and isopentenyl pyrophosphate (IPP), an intermediate in the self-mevalonate pathway. Infection with bacteria and protozoa using the MEP pathway leads to the rapid expansion of Vgamma2Vdelta2 T cells to very high numbers through preferential recognition of HMBPP. Activated Vgamma2Vdelta2 T cells produce proinflammatory cytokines and chemokines, kill infected cells, secrete growth factors for epithelial cells, and present antigens to alphabeta T cells. Vgamma2Vdelta2 T cells can also recognize high levels of IPP in certain tumors and in cells treated with pharmacological agents, such as bisphosphonates and alkylamines, that block farnesyl pyrophosphate synthase. Activated Vgamma2Vdelta2 T cells are able to kill most tumor cells because of recognition by T-cell receptor and natural killer receptors. The ubiquitous nature of the antigens converts essentially all Vgamma2Vdelta2 T cells to memory cells at an early age. Thus, primary infections with HMBPP-producing bacteria are perceived by Vgamma2Vdelta2 T cells as a repeat infection. Extensive efforts are underway to harness these cells to treat a variety of cancers and to provide microbial immunity. |
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Authors:
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Craig T Morita; Chenggang Jin; Ghanashyam Sarikonda; Hong Wang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review |
Journal Detail:
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Title: Immunological reviews Volume: 215 ISSN: 0105-2896 ISO Abbreviation: Immunol. Rev. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-02-12 Completed Date: 2007-03-29 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7702118 Medline TA: Immunol Rev Country: Denmark |
Other Details:
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Languages: eng Pagination: 59-76 Citation Subset: IM |
Affiliation:
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Division of Rheumatology, Department of Internal Medicine, Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. craig-morita@uiowa.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigen Presentation
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immunology* Diphosphates / immunology* Humans Immunologic Memory* Lymphocyte Activation / immunology Neoplasms / immunology Protein Prenylation / immunology* Receptors, Antigen, T-Cell, gamma-delta / immunology* T-Lymphocyte Subsets / immunology*, microbiology |
| Grant Support | |
ID/Acronym/Agency:
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AI057160/AI/NIAID NIH HHS; AR45504/AR/NIAMS NIH HHS; CA113874/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Diphosphates; 0/Receptors, Antigen, T-Cell, gamma-delta |
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