Nonpeptide Antigens, Presentation Mechanisms, and Immunological Memory of Human Vgamma2Vdelta2 T Cells: Discriminating Friend From Foe Through the Recognition of Prenyl Pyrophosphate Antigens

Immunol Rev. 2007 Feb;215:59-76. doi: 10.1111/j.1600-065X.2006.00479.x.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 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*
  • T-Lymphocyte Subsets / microbiology

Substances

  • Diphosphates
  • Receptors, Antigen, T-Cell, gamma-delta