Rebollo A, De Groote D, Baudrihay M, Thèze J, Jankovic D L
Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
Mol Immunol. 1992 Jan;29(1):119-30. doi: 10.1016/0161-5890(92)90163-r.
We have isolated and characterized 8 mAb against human rIL-2. All recognize nonglycosylated rIL-2 in liquid phase with similar affinities (Kd approximately 1 nM). Based on the epitopes of the IL-2 molecule that they recognize and their pattern of reactivity against glycosylated and non-glycosylated IL-2, they have been classified into four groups. The first group of anti-IL-2 mAb (2C4, 19B11 and 12C2) inhibits IL-2 binding to p70 IL-2R, while the second one (16F11, 18E1 and 2A4) prevents its binding to p55 IL-2R. These two groups neutralize IL-2 activity in a T cell proliferation assay equally well, due to their similar inhibition of IL-2 binding to high affinity IL-2R. Two mAb, 3H9 and 17F4, recognize separate epitopes on IL-2 molecule, are poor inhibitors of IL-2 binding, and they are inefficient in the neutralization of its biological activity; they have been assigned to the third and fourth groups, respectively. These results show that mAb from the first and second group recognize two epitopes of the human IL-2 molecule which probably overlap the p70 IL-2R and p55 IL-2R binding sites, respectively. In addition, these areas together form the high affinity IL-2R binding site. The two mAb from the third and fourth group recognized epitopes of IL-2 not directly involved in IL-2 binding to its receptor. All eight mAb anti-human IL-2 recognize murine IL-2 and with the exception of one, 17F4 mAb are also able to neutralize it in a T cell proliferation assay. The relationship between the structure and the function of the IL-2 molecule is discussed.
我们已分离并鉴定了8种抗人重组白细胞介素-2（rIL-2）的单克隆抗体（mAb）。所有这些抗体都能在液相中以相似的亲和力（解离常数Kd约为1 nM）识别非糖基化的rIL-2。根据它们所识别的IL-2分子表位以及它们对糖基化和非糖基化IL-2的反应模式，这些抗体被分为四组。第一组抗IL-2单克隆抗体（2C4、19B11和12C2）可抑制IL-2与p70 IL-2受体（IL-2R）的结合，而第二组（16F11、18E1和2A4）则可阻止其与p55 IL-2R的结合。由于它们对IL-2与高亲和力IL-2R结合的抑制作用相似，这两组抗体在T细胞增殖试验中对IL-2活性的中和效果同样良好。两种单克隆抗体3H9和17F4识别IL-2分子上不同的表位，对IL-2结合的抑制作用较弱，并且在中和其生物学活性方面效率不高；它们分别被归入第三组和第四组。这些结果表明，第一组和第二组的单克隆抗体分别识别了人IL-2分子的两个表位，这两个表位可能分别与p70 IL-2R和p55 IL-2R的结合位点重叠。此外，这些区域共同构成了高亲和力IL-2R的结合位点。第三组和第四组的两种单克隆抗体识别的IL-2表位不直接参与IL-2与其受体的结合。所有8种抗人IL-2单克隆抗体都能识别鼠IL-2，除了17F4单克隆抗体外，其他7种在T细胞增殖试验中也能够中和鼠IL-2。本文还讨论了IL-2分子的结构与功能之间的关系。
