MacKay R J, Socher S H
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610.
Am J Vet Res. 1992 Jun;53(6):921-4.
Antisera raised in rabbits against either purified recombinant-derived human tumor necrosis factor (TNF)- alpha (huTNF) or huTNF peptide-bovine thyroglobulin conjugates were evaluated for anti-equine TNF (eqTNF) activity. Binding and neutralizing anti-eqTNF activities were found in antisera raised against whole huTNF or against either of the peptides containing the N-terminal 15 amino acids of huTNF (huTNF[1-15] and huTNF[1-31]). Anti-eqTNF activity was not detected in antisera raised against huTNF[65-79], huTNF[98-111] or huTNF[124-141] peptides. The addition of excess huTNF[1-15] completely inhibited the ability of anti-huTNF[1-15] to bind eqTNF and reduced by approximately 25% the anti-eqTNF activity of an antiserum raised against whole huTNF. Nonconjugated huTNF[1-15] did not have eqTNF agonist or antagonist activity. Results were consistent with previous structural and functional data implicating the N-terminus of huTNF in receptor binding and indicate that the homologue of huTNF[1-15] on eqTNF may be a potentially important target for neutralizing anti-eqTNF antibodies.
对在兔体内产生的、针对纯化的重组人肿瘤坏死因子（TNF）-α（huTNF）或huTNF肽-牛甲状腺球蛋白缀合物的抗血清，评估其抗马TNF（eqTNF）活性。在针对完整huTNF或含有huTNF N端15个氨基酸的任何一种肽（huTNF[1-15]和huTNF[1-31]）产生的抗血清中，发现了结合和中和抗eqTNF活性。在针对huTNF[65-79]、huTNF[98-111]或huTNF[124-141]肽产生的抗血清中，未检测到抗eqTNF活性。添加过量的huTNF[1-15]完全抑制了抗huTNF[1-15]结合eqTNF的能力，并使针对完整huTNF产生的抗血清的抗eqTNF活性降低了约25%。未缀合的huTNF[1-15]没有eqTNF激动剂或拮抗剂活性。结果与先前涉及huTNF N端在受体结合中的结构和功能数据一致，并表明eqTNF上huTNF[1-15]的同源物可能是中和抗eqTNF抗体的一个潜在重要靶点。
