Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens.
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.
Morita
Craig T
CT
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
Jin
Chenggang
C
Sarikonda
Ghanashyam
G
Wang
Hong
H
D017951:Antigen Presentation / Q000276:immunology*; D011756:Diphosphates / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D017368:Protein Prenylation / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology
D011756:Diphosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta