ⓘ Non-peptidic antigen

                                     

ⓘ 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 -4-hydroxy-3-methyl-but-2-enyl pyrophosphate, a natural intermediate of the non-mevalonate pathway of isopentenyl pyrophosphate 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, but its effectiveness in vitro is 10.000-fold reduced, whether IPP represents a physiological signal of danger, 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, which are widely used for the treatment of osteoporosis and bone metastases, and act as Vy9 / Vδ2 T cell receptor agonists.

Certain alkylated Amines have been described for the activation of Vy9 / Vδ2 T cells in the laboratory, but only in millimolar concentrations, i.e., at energies of 10 6 times 8 10 times lower than those of HMB-PP, thereby questioning their physiological significance.