Document Detail


Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens.
MedLine Citation:
PMID:  17291279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Craig T Morita; Chenggang Jin; Ghanashyam Sarikonda; Hong Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Immunological reviews     Volume:  215     ISSN:  0105-2896     ISO Abbreviation:  Immunol. Rev.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-12     Completed Date:  2007-03-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7702118     Medline TA:  Immunol Rev     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  59-76     Citation Subset:  IM    
Affiliation:
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
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MeSH Terms
Descriptor/Qualifier:
Antigen Presentation / 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:
AI057160/AI/NIAID NIH HHS; AR45504/AR/NIAMS NIH HHS; CA113874/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Diphosphates; 0/Receptors, Antigen, T-Cell, gamma-delta

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