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Non-peptidic antigen



Non-peptidic antigens are low molecular weight compounds that stimulate human Vγ9/Vδ2 T cells. The most potent activator for Vγ9/Vδ2 T cells is (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate (IPP) biosynthesis. HMB-PP is an essential metabolite in most pathogenic bacteria including Mycobacterium tuberculosis as well as in malaria parasites, but is absent from the human host.

IPP itself is structurally closely related to HMB-PP and ubiquitously present in all living cells (i.e. also in human cells), yet its potency in vitro is 10,000-fold reduced; whether IPP represents a physiological 'danger' signal of stressed or transformed cells is still unclear.

Of pharmacological interest and with bioactivities comparable to that of IPP are synthetic aminobisphosphonates such as zoledronate (Zometa®) that are widely used to treat osteoporosis and bone metastases, and incidentally act as Vγ9/Vδ2 T cell receptor agonists.

Finally, certain alkylated amines have been described to activate Vγ9/Vδ2 T cells in vitro, however only at millimolar concentrations, i.e. with potencies 106-fold to 108-fold lower than those of HMB-PP, thereby questioning their physiological relevance.


References

  1. Morita CT, Mariuzza RA, Brenner MB. Antigen recognition by human γδ T cells: pattern recognition by the adaptive immune system. Springer Semin Immunopathol. 2000;22:191-217. PMID 11116953
  2. Eberl M, Hintz M, Reichenberg A, Kollas AK, Wiesner J, Jomaa H. Microbial isoprenoid biosynthesis and human γδ T cell activation. FEBS Lett. 2003;544:4-10. PMID 12782281
  3. Holtmeier W, Kabelitz D. γδ T cells link innate and adaptive immune responses. Chem Immunol Allergy. 2005;86:151-83. PMID 15976493
  4. Girardi M. Immunosurveillance and immunoregulation by γδ T cells. J Invest Dermatol. 2006 Jan;126:25-31. PMID 16417214
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Non-peptidic_antigen". A list of authors is available in Wikipedia.
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