Christensen P A, Danielczyk A, Ravn P, Stahn R, Karsten U, Goletz S
Glycotope GmbH, Robert-Rössle-Str. 10, Berlin-Buch, Germany.
Scand J Immunol. 2007 Apr;65(4):362-7. doi: 10.1111/j.1365-3083.2007.01913.x.
Antibodies to either peptide or carbohydrate tumour antigens are established tools for diagnostics and therapy. We here describe an antibody (A70-A/A9) recognizing a carbohydrate epitope common to the tumour-associated Lewis Y and Lewis b antigens (Fucalpha1-2Galbeta1-4/3[Fucalpha1-3/4]GlcNAcbeta-). Its specificity was established without doubt with a panel of 86 synthetic mono- and oligosaccharidic structures. This antibody was found to cross-react with the nuclear protein histone H1. Binding to H1 was specific, periodate-insensitive (non-carbohydrate) and saturable. Histone H1 was able to inhibit Lewis Y binding very effectively in a concentration-dependent manner. We conclude that it represents an example of natural peptide mimicry of a carbohydrate epitope. It may explain the observed occurrence of 'anti-histone autoantibodies' in cancer patients.
针对肽或碳水化合物肿瘤抗原的抗体是诊断和治疗的既定工具。我们在此描述一种抗体(A70-A/A9),它识别肿瘤相关的Lewis Y和Lewis b抗原共有的碳水化合物表位(Fucα1-2Galβ1-4/3[Fucα1-3/4]GlcNAcβ-)。通过一组86种合成单糖和寡糖结构,毫无疑问地确定了其特异性。发现该抗体与核蛋白组蛋白H1发生交叉反应。与H1的结合是特异性的、对高碘酸盐不敏感(非碳水化合物)且可饱和的。组蛋白H1能够以浓度依赖的方式非常有效地抑制Lewis Y结合。我们得出结论,它代表了碳水化合物表位天然肽模拟的一个例子。这可能解释了在癌症患者中观察到的“抗组蛋白自身抗体”的出现。