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 (''E'')-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) is an intermediate of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis. The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-''C''-methyl ...

), a natural intermediate of the non-mevalonate pathway of

isopentenyl pyrophosphate Isopentenyl pyrophosphate (IPP, isopentenyl diphosphate, or IDP) is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway (commonly called the mevalonate pathway) and in the ''non-mevalonate'' MEP pathway of i ...

(IPP) biosynthesis.

is an essential metabolite in most pathogenic bacteria including '' Mycobacterium tuberculosis'' as well as in

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

parasites, but is absent from the human host. IPP itself is structurally closely related to

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 Zoledronic acid, also known as zoledronate and sold under the brand name Zometa by Novartis among others, is a medication used to treat a number of bone diseases. These include osteoporosis, high blood calcium due to cancer, bone breakdown due ...

(Zometa) that are widely used to treat osteoporosis and bone

metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then ...

, and act as Vγ9/Vδ2 T cell receptor agonists. Certain alkylated

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

s 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

, thereby questioning their physiological relevance.

References

#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. #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. #Holtmeier W, Kabelitz D. ''γδ T cells link innate and adaptive immune responses.'' Chem Immunol Allergy. 2005;86:151-83. #Girardi M. Immunosurveillance and immunoregulation by γδ T cells. J Invest Dermatol. 2006 Jan;126:25-31. {{PMID, 16417214 Immune system T cells