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VH互补决定区2(VH CDR2)中的氨基酸替换改变了独特型,但未改变单克隆抗体与α(1→6)葡聚糖的抗原结合。

Amino acid substitutions in VH CDR2 change the idiotype but not the antigen-binding of monoclonal antibodies to alpha(1----6)dextrans.

作者信息

Sikder S K, Borden P, Gruezo F, Akolkar P N, Bhattacharya S B, Morrison S L, Kabat E A

机构信息

Department of Microbiology, College of Physicians and Surgeons, Columbia University, NY 10032.

出版信息

J Immunol. 1989 Feb 1;142(3):888-93.

PMID:2464031
Abstract

An idiotype defined by mAb and polyclonal antibodies to 10.16.1, an anti-alpha(1----6) dextran was previously reported to be expressed on most BALB/c anti-alpha(1----6)dextrans with groove-type sites and to involved CDR3 and probably CDR2. By comparing amino acid sequences of VH and VL derived from cDNA of idiotype+ and idiotype- anti-alpha(1----6)dextran hybridoma proteins, an idiotope was assigned to VH CDR2. Substitution of phenylalanine for leucine at residue 52 in CDR2 coupled with amino acid changes at either residue 58 or residues 57 and 60 abolished expression of this idiotype without affecting Ag binding.

摘要

一种由针对10.16.1(一种抗α(1→6)葡聚糖)的单克隆抗体和多克隆抗体所定义的独特型,先前报道在大多数具有沟槽型位点的BALB/c抗α(1→6)葡聚糖上表达,并且涉及互补决定区3(CDR3),可能还涉及互补决定区2(CDR2)。通过比较源自独特型阳性和独特型阴性抗α(1→6)葡聚糖杂交瘤蛋白cDNA的重链可变区(VH)和轻链可变区(VL)的氨基酸序列,一个独特位被定位到VH CDR2。在CDR2的第52位残基处用苯丙氨酸取代亮氨酸,再加上第58位残基或第57和60位残基处的氨基酸变化,消除了这种独特型的表达,而不影响抗原结合。

相似文献

1
Amino acid substitutions in VH CDR2 change the idiotype but not the antigen-binding of monoclonal antibodies to alpha(1----6)dextrans.VH互补决定区2(VH CDR2)中的氨基酸替换改变了独特型,但未改变单克隆抗体与α(1→6)葡聚糖的抗原结合。
J Immunol. 1989 Feb 1;142(3):888-93.
2
Variable region cDNA sequences and antigen binding specificity of mouse monoclonal antibodies to isomaltosyl oligosaccharides coupled to proteins. T-dependent analogues of alpha(1----6)dextran.与蛋白质偶联的异麦芽糖基寡糖的小鼠单克隆抗体的可变区cDNA序列及抗原结合特异性。α(1→6)葡聚糖的T细胞依赖性类似物。
J Immunol. 1989 Feb 1;142(3):863-70.
3
Complete heavy and light chain variable region sequence of anti-arsonate monoclonal antibodies from BALB/c and A/J mice sharing the 36-60 idiotype are highly homologous.来自BALB/c和A/J小鼠、具有36-60独特型的抗砷酸盐单克隆抗体的完整重链和轻链可变区序列高度同源。
J Immunol. 1984 Nov;133(5):2603-9.
4
Sequences of variable regions of hybridoma antibodies to alpha (1----6) dextran in BALB/c and C57BL/6 mice.BALB/c和C57BL/6小鼠中抗α(1→6)葡聚糖杂交瘤抗体可变区的序列
J Immunol. 1985 Dec;135(6):4215-21.
5
Two families of monoclonal antibodies to alpha(1----6)dextran, VH19.1.2 and VH9.14.7, show distinct patterns of J kappa and JH minigene usage and amino acid substitutions in CDR3.针对α(1→6)葡聚糖的两个单克隆抗体家族,VH19.1.2和VH9.14.7,在CDR3中显示出Jκ和JH小基因使用及氨基酸取代的不同模式。
J Immunol. 1990 Nov 1;145(9):3002-10.
6
Amino acid sequence of a phosphocholine-binding antibody from an immune defective CBA/N mouse employing the T15 VH region associated with unusual DH, JH, and V kappa segments.利用与异常重链多样性基因(DH)、重链连接基因(JH)和κ轻链可变区(Vκ)片段相关的T15重链可变区(VH),从免疫缺陷的CBA/N小鼠中获得的一种磷酸胆碱结合抗体的氨基酸序列。
J Immunol. 1984 Mar;132(3):1544-9.
7
The specificities of polyclonal and monoclonal anti-idiotypes to anti-alpha(1----6)dextrans; possible correlations of idiotype with amino acid sequence.多克隆和单克隆抗独特型针对抗α(1→6)葡聚糖的特异性;独特型与氨基酸序列的可能相关性。
Mol Immunol. 1988 Mar;25(3):251-62. doi: 10.1016/0161-5890(88)90016-8.
8
Different VL and VH germ-line genes are used to produce similar combining sites with specificity for alpha(1----6)dextrans.不同的VL和VH种系基因被用于产生对α(1→6)葡聚糖具有特异性的相似结合位点。
J Immunol. 1987 Jun 15;138(12):4472-9.
9
The effect of isotype and the J kappa region on antigen binding and idiotype expression by antibodies binding alpha (1----6) dextran.同种型和Jκ区域对结合α(1→6)葡聚糖的抗体的抗原结合及独特型表达的影响。
J Immunol. 1989 Feb 15;142(4):1235-44.
10
Specificity and variable region cDNA sequence of an isogeneic monoclonal antiidiotype to an anti-alpha(1----6)dextran.抗α(1→6)葡聚糖同基因单克隆抗独特型抗体的特异性及可变区cDNA序列
Mol Immunol. 1991 Apr-May;28(4-5):505-15. doi: 10.1016/0161-5890(91)90165-g.

引用本文的文献

1
Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment.利用VH4-21基因片段对人免疫球蛋白上一种交叉反应性独特型表位进行分子特征分析。
J Exp Med. 1993 Oct 1;178(4):1419-28. doi: 10.1084/jem.178.4.1419.
2
Content and dynamics of the human antibody variable region repertoire to the Haemophilus influenzae type b polysaccharide.针对b型流感嗜血杆菌多糖的人类抗体可变区库的内容及动态变化
Springer Semin Immunopathol. 1993;15(2-3):119-37. doi: 10.1007/BF00201096.
3
A fetally expressed immunoglobulin VH1 gene belongs to a complex set of alleles.
一个在胎儿期表达的免疫球蛋白VH1基因属于一组复杂的等位基因。
J Clin Invest. 1993 Jun;91(6):2358-67. doi: 10.1172/JCI116468.
4
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Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2502-6. doi: 10.1073/pnas.91.7.2502.