Non-peptidic antigen
Encyclopedia
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 act as Vγ9/Vδ2 T cell receptor agonists.
Certain alkylated amine
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 HMB-PP, thereby questioning their physiological relevance.
Non-mevalonate pathway
The non-mevalonate pathway or 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis is an alternative metabolic pathway leading to the formation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate that has been elucidated only...
of isopentenyl pyrophosphate
Isopentenyl pyrophosphate
Isopentenyl pyrophosphate is an intermediate in the classical, HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes and terpenoids. IPP is formed from acetyl-CoA via mevalonic acid...
(IPP) biosynthesis. HMB-PP is an essential metabolite in most pathogenic bacteria including Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
as well as in malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
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
Zoledronate
Zoledronic acid or zoledronate is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer, as well as for treating osteoporosis...
(Zometa) that are widely used to treat osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
and bone metastases, and act as Vγ9/Vδ2 T cell receptor agonists.
Certain alkylated amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
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 HMB-PP, thereby questioning their physiological relevance.