A disulfide conjugate between anti-tetanus antibodies and HIV (37-72)Tat neutralizes tetanus toxin inside chromaffin cells

Conjugates between anti-tetanus F(ab')(2) fragments and the (37-72) fragmen t of the HIV Tat protein were taken up by chromaffin cells, NG108-15 neuroh ybridoma cells and Rev-2-T-6 lymphoma cells. The uptake could not be inhibi ted by competition with (37-72)Tat, but was reduced in the presence of meta bolic inhibitors or at tory temperature, The disulfide as well as the thioe ther conjugate were translocated to the cytoplasmic space, but only the dis ulfide conjugate moderately restored the stimulated transmitter release inh ibited by tetanus toxin, Therefore, disulfide conjugates are more promising than thioethers for the neutralization of intracellular antigens, These co njugates provide nerv tools to study neuroprotection against bacterial neur otoxins. (C) 1999 Federation of European Biochemical Societies.