Mapping of the Alz 50 epitope in microtubule-associated proteins tau.
Alz 50 and seven other monoclonal antibodies have been shown to react with both tau and Alzheimer brain proteins of molecular mass 60-70 kDa. The location of some of the epitopes of these antibodies (Alz 50, Tau-2, NP14, Ab 636.7) on the tau molecule is unknown, whereas those of others (Tau 60, Tau 14, Tau-1, Tau 46) have recently been demonstrated in fetal human tau at amino acid residues 60-72, 83-120, 131-140, and 315-352. To determine the location of the unknown epitopes, human tau was digested with chymotrypsin and trypsin, and the bovine microtubule fraction was incubated with chymotrypsin. Comparison of the immunoblots of chymotryptic digested tau with those of untreated preparations showed that the Alz 50 epitope was more sensitive than other tau epitopes to proteolysis. Cleavage of a 3-4 kDa polypeptide from the periphery of tau was sufficient to remove the Alz 50 epitope, but not the epitopes of Tau 46 (C-end) or Tau 60 (N-end). The distribution of the Alz 50 epitope in endogenously degraded, chymotrypsin or trypsin digested tau fragments was different from that of the Tau 46 epitope known to be located within 38 residues from the C-terminus of the tau molecule. Based on these observations Alz 50 epitope was considered to be located within 3-4 kDa of the N-terminus of tau. A comparison of immunoblots of different tau-reactive antibodies showed similarities between Tau 60 and Tau-2, and between Tau 14, Tau-1, NP14, and Ab 636.7.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.
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Chien
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Lee
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Yen
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D002417:Cattle; D002918:Chymotrypsin; D000939:Epitopes; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D008870:Microtubules / Q000276:immunology*; D010449:Peptide Mapping; D051381:Rats; D013045:Species Specificity; D014357:Trypsin; D016875:tau Proteins
C056167:Alzheimer's disease antigen; D000911:Antibodies, Monoclonal; D000941:Antigens; D000939:Epitopes; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D002918:Chymotrypsin; D014357:Trypsin