期刊文献+

抗乙酰胆碱受体单链抗体对致病性抗体结合活性的抑制作用

Suppressive Effect of the Single Chain Antibody Against Acetylcholine Receptor on the Binding Activity of the Pathogenic Antibodies
暂未订购
导出
摘要 为探讨单链抗体 (ScFv )对重症肌无力 (MG )的特异性免疫治疗作用 ,从分离自MG患者胸腺的抗乙酰胆碱受体(AchR )抗原结合片段Fab6 37构建单链抗体ScFv6 37。应用放射免疫测定法测定了ScFv6 37与刺激抗原人AchR的特异性结合活性以及与相关抗原大鼠AchR和电鳐AchR的交叉反应 ,应用竞争性ELISA测定抑制致病性抗AchR完整抗体IgG6 37与人AchR结合活性。结果发现ScFv6 37只能与人AchR结合 ,不能与大鼠和电鳐的AchR结合。对IgG6 37与人AchR结合的抑制率为 17 5 %~ 32 9%。表明单链抗体对AchR具有一定的“保护”作用。 To investigate the specific suppressive effect of the antibody against the single chain variable fragment (ScFv) on myathenia gravis (MG), ScFv637 was constructed from the antigen-binding fragment 637 (Fab637) of anti-acetylcholine receptor (AchR) antibody derived from thymus of a patient suffered from MG. The specific binding activity of ScFv637 with the human AchR of stimulating antigen (hAchR) and the cross-reactions with the rat AchR of related antigens (rAchR) and torpede AchR (tAchR) were determined by radioimmunoassay (RTA). The suppressive effect of ScFv637 on the binding activity of the pathogenic intact antibody against AchR was measured by competitive ELISA. It was found that ScFv6378 could bind with hAChR, but was unable to bind with rAchR or tAchR. Furthermore, it was also capable to inhibit the binding with the pathogenic anti AchR antibody IgG637 against hAchR by 17.5%~32.9%, indicating that ScFv637 has a protective effect on hAchR, which holds promise for the immunotherapy of ScFv in patients with MG.
出处 《现代免疫学》 CAS CSCD 北大核心 2004年第3期235-237,244,共4页 Current Immunology
基金 国家自然科学基金资助项目 ( 3 9960 0 72 )
关键词 重症肌无力 单链抗体 乙酰胆碱受体 myasthenia gravis single chain variable fragment acetylcholine receptors
  • 相关文献

参考文献11

  • 1Lindstrom J,Merlie J,Yogeeswaran G. Biochemical properties of acetylcholine receptor subunits from Torpedo Californica[J]. Biochemistry,1979,18:4465.
  • 2Tzartos SJ, Selbold ME, Lindstrom JM. Specificities of antibodies to acetylcholine receptor in sera from myasthenia gravis patients measured by monoclonal antibodies[J]. Proc Natl Acad Sci USA, 1982,79:188.
  • 3Luther MA, Schoepfer R, Whiting P, et al. A muscle acetylcholine receptor is expressed in the human cerebellar medulloblastoma cell line TE671[J]. J Neurosci, 1989,9:1082.
  • 4Graus Y, de Baets M, Parren P, et al. Human anti-nicotinic acetylcholine receptor recombinant Fab fragments isolated from thymus-derived phage display libraries from myasthenia gravis patients reflect predominant specificities in serum and block the actio
  • 5de Wildt R, Finnem R, Ouwehand W, et al.Characterization of human variable domain antibody fragments against the U1 RNA-associated A protein, selected from a synthetic and a patient-derived combinatoral V gene library[J]. Eur J Immunol, 1996,26:629.
  • 6Souroujon M, Pachner A, Fuchs S. The treatment of passively transferred experimental myasthenia with anti-idiotypic antibodies[J]. Neurology, 1986,36:622.
  • 7Im SH, Barchan D, Souroujon MC, et al. Role of tolerogen conformation in induction of oral tolerance in experimental autoimmune myasthenia gravis[J]. J Immunol, 2000,165:3599.
  • 8Monfardini C, Milani M, Ostlie N, et al. Adoptive protection from experimental autoimmune myasthenia gravis with T cells from mice treated nasally with acetylcholine receptor epitopes[J]. J Neuroimmunol, 2002,123:123.
  • 9Roggenbuck D,Konig H,Niemann B,et al. Real-time biospecific interaction analysis of a natural human polyreactive monoclonal IgM antibody and its Fab and ScFv fragments with several antigens[J]. Scanad J Immunol,1994,40:64.
  • 10Tzartos SJ, Kokia A, Walgrave S, et al. Localization of the main immunogenic region of the human muscle acetylcholine receptor to residues 67-76 of the α-subunit[J]. Proc Natl Acad Sci USA, 1998,85:2899.

二级参考文献8

  • 1Graus Y, de Baets M. Myasthenia gravis: An autoim mune response against the acetylcholine receptor [J].Immunological Res, 1993,12: 78.
  • 2Tzartos SJ, Seybold ME, Lindstrom JM. Specificities of antibodies to acetylcholine receptors in sera from myas thenia gravis patients measured by monoclonal antibodies[J]. Proc Natl Acad Sci USA, 1982,79:188.
  • 3Graus Y, de Baets M, Parren P, et al.. Human antinicotinic acetylcholine receptor recombinant Fab frag ments isolated from thymus-derived phage display libraries from myasthenia gravis patients reflect predomi nant specificities in serum and block the action of pathogenic serum antibodies[J]. J Immunol, 1997,158:1919.
  • 4Papanastasiou D, Mamalaki A, Eliopoulos E, et al.. Construction and characterization of an humanized single chain Fv antibody fragment against the main immunogenic region of the acetylcholine receptor[J]. J Neuroim munol, 1999,94:182.
  • 5Mamalaki A, Trakas N, Tzartos SJ. Bacterial expression of single-chain Fy fragment which efficiently protects the acetylcholine receptor against antigenic modulation caused by myasthenic antibodies[J]. Eur J Immunol, 1993,23: 1839.
  • 6Tsantili P, Tzartos SJ, Mamalaki A. High affinity sin gle-chain antibody fragments protecting the human nico tinic acetylcholine receptor [J]. J Neuroimmunol , 1999,94:15.
  • 7Tripathi PK, Qin H, Deng S, et al.. Antigen mimicry by an anti-idiotypic antibody single chain variable frag ment [ J ]. Mol Immunol, 1998,35 (13): 853.
  • 8杨康鹃,孟繁平,YGraus,MdeBaets.重组质粒对大肠杆菌 DH5_α 的转化[J].延边大学医学学报,1997,20(2):69-70. 被引量:3

共引文献5

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部