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重链和轻链以及结合位点对小鼠抗谷氨酸脱羧酶抗体独特型特异性的贡献。

Contribution of the H- and L-chains and of the binding site to the idiotypic specificities of mouse anti-GAT antibodies.

作者信息

Sommé G, Serra J R, Leclercq L, Moreau J L, Mazie J C, Moinier D, Fougerèau M, Thèze J

出版信息

Mol Immunol. 1982 Aug;19(8):1011-9. doi: 10.1016/0161-5890(82)90309-1.

DOI:10.1016/0161-5890(82)90309-1
PMID:6813679
Abstract

The contribution of the H- and L-chains to the structure of the main idiotype of anti-poly (Glu60-Ala30-Tyr10) (GAT) antibodies has been studied. This idiotype has been previously divided into four types of specificity: (1) the highly conserved idiotypic specificity (h.c. GAT) is expressed by anti-GAT antibodies from the guinea-pig, rat and mice; (2) the public specificity (p. GAT) is expressed in an identical form by all anti-GAT antibodies from all strains of mice tested and by all hybridoma products (HP) with anti-GAT activity; (3) the strain-restricted specificity (s.r. GAT-1) is only expressed by anti-GAT antibodies from strains with Ig-1a, Ig-1c and Ig-1c allotypic markers; and finally (4) the individual specificity i1-GAT defined on HP G5 is also expressed by most of the hybridoma protein with anti-poly (Glu50-Tyr50) (GT) activity. In this paper we show that h.c.GAT, p.GAT and i1-GAT require the interaction of H- and L-chains to be expressed: (1) isolated H- and L-chains from HP G5 did not express these specificities; and (2) recombinant molecules composed of H- and L-chains from HP with anti-GAT activity and an irrelevant myeloma protein (MOPC21) never expressed h.c.GAT, p.GAT and i1-GAT. We next investigated the relationship between the GAT binding site and the p.GAT, h.c.GAT and s.r.GAT-1 idiotypic specificities. GAT and GT were not able to inhibit the binding to s.r.GAT-1 while they inhibit the idiotypic binding to p.GAT and h.c.GAT. A GAT fragment of mol. wt 3000 was also shown to inhibit the binding of p.GAT and h.c.GAT to the appropriate sera. Thus p.GAT and h.c.GAT are very close to the GAT combining site while s.r.GAT-1 represents an idiotypic specificity located outside the GAT binding site.

摘要

已对重链和轻链在抗聚(Glu60 - Ala30 - Tyr10)(GAT)抗体主要独特型结构中的作用进行了研究。此前已将这种独特型分为四种特异性类型:(1)高度保守的独特型特异性(h.c. GAT)由豚鼠、大鼠和小鼠的抗GAT抗体表达;(2)共有特异性(p. GAT)由所有测试小鼠品系的所有抗GAT抗体以及所有具有抗GAT活性的杂交瘤产物(HP)以相同形式表达;(3)品系限制特异性(s.r. GAT - 1)仅由具有Ig - 1a、Ig - 1c和Ig - 1c同种异型标记的品系的抗GAT抗体表达;最后(4)在HP G5上定义的个体特异性i1 - GAT也由大多数具有抗聚(Glu50 - Tyr50)(GT)活性的杂交瘤蛋白表达。在本文中,我们表明h.c.GAT、p.GAT和i1 - GAT需要重链和轻链相互作用才能表达:(1)从HP G5分离的重链和轻链不表达这些特异性;(2)由具有抗GAT活性的HP的重链和轻链与无关骨髓瘤蛋白(MOPC21)组成的重组分子从未表达h.c.GAT、p.GAT和i1 - GAT。接下来,我们研究了GAT结合位点与p.GAT、h.c.GAT和s.r.GAT - 1独特型特异性之间的关系。GAT和GT不能抑制与s.r.GAT - 1的结合,而它们能抑制与p.GAT和h.c.GAT的独特型结合。一个分子量为3000的GAT片段也被证明能抑制p.GAT和h.c.GAT与相应血清的结合。因此,p.GAT和h.c.GAT非常接近GAT结合位点,而s.r.GAT - 1代表位于GAT结合位点之外的独特型特异性。

相似文献

1
Contribution of the H- and L-chains and of the binding site to the idiotypic specificities of mouse anti-GAT antibodies.重链和轻链以及结合位点对小鼠抗谷氨酸脱羧酶抗体独特型特异性的贡献。
Mol Immunol. 1982 Aug;19(8):1011-9. doi: 10.1016/0161-5890(82)90309-1.
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引用本文的文献

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BALB/c antiarsonate idiotypes: gene complementation necessary for expression.BALB/c抗砷酸盐独特型:表达所需的基因互补。
Immunogenetics. 1984;20(4):417-32. doi: 10.1007/BF00345616.
2
Analysis of antibody diversity: V-D-J mRNA nucleotide sequence of four anti-GAT monoclonal antibodies. A paucigene system using alternate D-J recombinations to generate functionally similar hypervariable regions.抗体多样性分析:四种抗GAT单克隆抗体的V-D-J mRNA核苷酸序列。一种利用交替D-J重组产生功能相似高变区的寡基因系统。
EMBO J. 1983;2(6):867-72. doi: 10.1002/j.1460-2075.1983.tb01515.x.
3
V kappa gene family in (Glu60 Ala30 Tyr10)n (GAT)-specific antibodies that express CGAT (or pGAT) public idiotypic specificities. Protein and mRNA sequencing of eight monoclonal V kappa chains.
表达CGAT(或pGAT)公共独特型特异性的(Glu60 Ala30 Tyr10)n(GAT)特异性抗体中的Vκ基因家族。八条单克隆Vκ链的蛋白质和mRNA测序。
J Exp Med. 1983 Nov 1;158(5):1415-27. doi: 10.1084/jem.158.5.1415.
4
Immunoglobulin diversity: analysis of the germ-line VH gene repertoire of the murine anti-GAT response.免疫球蛋白多样性:对小鼠抗GAT反应的种系VH基因库的分析。
Nucleic Acids Res. 1983 Jun 25;11(12):4007-17. doi: 10.1093/nar/11.12.4007.
5
Investigation of the idiotypic determinants of IgM monoclonal proteins associated with neuropathy.与神经病变相关的IgM单克隆蛋白独特型决定簇的研究。
Clin Exp Immunol. 1984 Sep;57(3):621-5.
6
Structural bases for public idiotypic specificities of monoclonal antibodies directed against poly(Glu60Ala30Tyr10) and poly(Glu60Ala40) random copolymers.针对聚(Glu60Ala30Tyr10)和聚(Glu60Ala40)无规共聚物的单克隆抗体的公共独特型特异性的结构基础
Proc Natl Acad Sci U S A. 1983 May;80(10):3040-4. doi: 10.1073/pnas.80.10.3040.
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Interstrain conservation of the murine GAT-specific antibody V kappa repertoire as analyzed at the germline gene level.在种系基因水平分析的小鼠GAT特异性抗体Vκ基因库的品系间保守性。
EMBO J. 1983;2(10):1771-6. doi: 10.1002/j.1460-2075.1983.tb01656.x.
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The idiotypic network and the internal image: possible regulation of a germ-line network by paucigene encoded Ab2 (anti-idiotypic) antibodies in the GAT system.独特型网络与内影像:在GAT系统中,寡基因编码的Ab2(抗独特型)抗体对种系网络的可能调控。
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