Idusogie E E, Wong P Y, Presta L G, Gazzano-Santoro H, Totpal K, Ultsch M, Mulkerrin M G
Oncology Department, Aventis-Gencell, Hayward, CA 94545, USA.
J Immunol. 2001 Feb 15;166(4):2571-5. doi: 10.4049/jimmunol.166.4.2571.
This manuscript describes two sites in a human IgG1 that, when mutated individually or in combination, result in a dramatic increase in C1q binding and complement-dependent cytotoxicity activity. These two residues, K326 and E333, are located at the extreme ends of the C1q binding epicenter in the C(H)2 domain of a human IgG. A mutation to tryptophan at K326 debilitates Ab-dependent cell-mediated cytotoxicity activity. In addition, substitutions of the residues E333 with serine and of K326 with tryptophan in a human IgG2 confer biological activity in the complement-dependent cytotoxicity assay in which the wild-type IgG2 is inactive. This study reveals that the residues K326 and E333 play a significant role in the control of the biological activity of an IgG molecule and can rescue the activity of an inactive IgG isotype.
本手稿描述了人IgG1中的两个位点，当单独或组合突变时，会导致C1q结合和补体依赖性细胞毒性活性显著增加。这两个残基K326和E333位于人IgG的C(H)2结构域中C1q结合中心的两端。K326突变为色氨酸会削弱抗体依赖性细胞介导的细胞毒性活性。此外，在人IgG2中，将残基E333替换为丝氨酸以及将K326替换为色氨酸，在野生型IgG2无活性的补体依赖性细胞毒性试验中赋予了生物活性。这项研究表明，残基K326和E333在控制IgG分子的生物活性中起重要作用，并且可以挽救无活性IgG同种型的活性。
