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) fragment of the HIV Tat protein were taken up by chromaffin cells, NG108-15 neurohybridoma cells and Rev-2-T-6 lymphoma cells. The uptake could not be inhibited by competition with (37-72)Tat, but was reduced in the presence of metabolic inhibitors or at low temperature. The disulfide as well as the thioether conjugate were translocated to the cytoplasmic space, but only the disulfide conjugate moderately restored the stimulated transmitter release inhibited by tetanus toxin. Therefore, disulfide conjugates are more promising than thioethers for the neutralization of intracellular antigens. These conjugates provide new tools to study neuroprotection against bacterial neurotoxins.
Stein
S
S
Institute of Legal Medicine, University of Hamburg, Germany.
Weiss
A
A
Adermann
K
K
Lazarovici
P
P
Hochman
J
J
Wellhöner
H
H
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002232:Carbocyanines; D002417:Cattle; D019439:Chromaffin Cells / Q000276:immunology / Q000378:metabolism*; D004220:Disulfides / Q000276:immunology*; D005089:Exocytosis / Q000187:drug effects; D015696:Gene Products, tat / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008856:Microscopy, Fluorescence; D009638:Norepinephrine / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D013440:Sulfides / Q000276:immunology; D013744:Tetanus Toxin / Q000276:immunology* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D054322:tat Gene Products, Human Immunodeficiency Virus
D000906:Antibodies; D002232:Carbocyanines; D004220:Disulfides; D015696:Gene Products, tat; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D013440:Sulfides; D013744:Tetanus Toxin; C089187:cyanine dye 3; D054322:tat Gene Products, Human Immunodeficiency Virus; C109668:tat peptide (32-72), Human immunodeficiency virus 1; D009638:Norepinephrine