Kumar Sanjeev, Nagl Sylvia, Kalsi J K, Ravirajan C T, Athwal Dee, Latchman David S, Pearl Laurence H, Isenberg David A
Bloomsbury Rheumatology Unit, Department of Medicine, Centre for Rheumatology, University College London Hospital, Arthur Stanley House, 40-50 Tottenham Street, London W1P 9PG, UK.
Mol Immunol. 2003 Dec;40(8):517-30. doi: 10.1016/s0161-5890(03)00225-6.
We have recently shown that the human anti-DNA antibodies B3 and 33H11 also bind cardiolipin and that the anti-autoantigen activity resides predominantly on their lambda light chains. We now show that the two auto-antibodies possess strong reactivity to the plasma-protein 2-Glycoprotein I (beta2-GPI) also. Utilizing chain shuffling experiments involving an unrelated anti-p185 antibody 4D5 with insignificant reactivity to cardiolipin or to beta2-GPI, we now demonstrate that hybrid Fabs with constituent light chain, but not the heavy chain, of B3 or 33H11, exhibit anti-cardiolipin activity. Furthermore, the constructs possessing the auto-antibody-derived light chain also exhibited significant reactivity to beta2-GPI. The results suggest that anti-DNA, anti-cardiolipin and anti-beta2-GPI activities co-exist on the light chains of the antibodies studied and, importantly, these activities could be transferred to antibody constructs by their light chains alone. Computer-generated models of the three-dimensional structures of the auto-antibodies and their hybrids, suggest predominant interaction of their light chains with domain IV of beta2-GPI.
我们最近发现，人类抗DNA抗体B3和33H11也能结合心磷脂，且其抗自身抗原活性主要存在于它们的λ轻链上。我们现在发现，这两种自身抗体对血浆蛋白2-糖蛋白I（β2-GPI）也具有很强的反应性。利用链置换实验，将与心磷脂或β2-GPI反应性不显著的无关抗p185抗体4D5参与其中，我们现在证明，具有B3或33H11组成性轻链而非重链的杂交Fabs表现出抗心磷脂活性。此外，拥有源自自身抗体轻链的构建体对β2-GPI也表现出显著反应性。结果表明，抗DNA、抗心磷脂和抗β2-GPI活性共存于所研究抗体的轻链上，重要的是，这些活性仅通过其轻链就能转移到抗体构建体上。自身抗体及其杂交体三维结构的计算机生成模型表明，它们的轻链与β2-GPI的结构域IV主要相互作用。
