针对蛋白质表位中单个氨基酸互换具有特异性的抗体使用结构不同的可变区。
Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions.
作者信息
Stark S E, Caton A J
机构信息
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
出版信息
J Exp Med. 1991 Sep 1;174(3):613-24. doi: 10.1084/jem.174.3.613.
Abstract
We have analyzed how the immune system generates antibodies that are specific for analogues of an epitope on the influenza virus hemagglutinin (HA) that differ solely by the presence of Asp or Gly at amino acid 225. Most antibodies induced in response to HA(Asp225) use one of a few closely related variable (V) region structures that are encoded by characteristic VH/Vk gene segment combinations. Remarkably, none of these VH/Vk combinations was induced in response to HA(Gly225). Instead of modifying the HA(Asp225)-specific V regions by junctional variation or somatic mutation to recognize the altered epitope, new VH/Vk combinations were used. The expression of unique VH/Vk combinations appears to confer exquisite specificity to the selection of HA-specific B cells from the pre-immune repertoire.
摘要
我们分析了免疫系统如何产生针对流感病毒血凝素（HA）上一个表位类似物的特异性抗体，这些类似物仅在氨基酸225处存在天冬氨酸（Asp）或甘氨酸（Gly）而有所不同。大多数针对HA（Asp225）诱导产生的抗体使用由特征性VH/Vk基因片段组合编码的少数几种密切相关的可变（V）区结构之一。值得注意的是，这些VH/Vk组合中没有一种是针对HA（Gly225）诱导产生的。不是通过连接多样性或体细胞突变来修饰HA（Asp225）特异性V区以识别改变的表位，而是使用了新的VH/Vk组合。独特的VH/Vk组合的表达似乎赋予了从免疫前库中选择HA特异性B细胞的高度特异性。
相似文献
1
Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions.针对蛋白质表位中单个氨基酸互换具有特异性的抗体使用结构不同的可变区。
J Exp Med. 1991 Sep 1;174(3):613-24. doi: 10.1084/jem.174.3.613.
2
3
4
V region gene usage and somatic mutation in the primary and secondary responses to influenza virus hemagglutinin.流感病毒血凝素初次和二次应答中的V区基因使用及体细胞突变
J Immunol. 1990 Apr 1;144(7):2795-801.
5
6
Molecular characterization and structural modeling of immunoglobulin variable regions from murine monoclonal antibodies specific for hepatitis B virus surface antigen.针对乙型肝炎病毒表面抗原的鼠源单克隆抗体免疫球蛋白可变区的分子特征及结构建模
Mol Immunol. 1993 Oct;30(14):1295-306. doi: 10.1016/0161-5890(93)90046-e.
7
Activation and negative selection of functionally distinct subsets of antibody-secreting cells by influenza hemagglutinin as a viral and a neo-self antigen.流感血凝素作为病毒抗原和新自身抗原对功能不同的抗体分泌细胞亚群的激活和阴性选择。
J Exp Med. 1996 Jan 1;183(1):13-26. doi: 10.1084/jem.183.1.13.
8
9
Immunodominance with progenitor B cell diversity in the neutralizing antibody repertoire to influenza infection.流感感染中和抗体库中祖B细胞多样性与免疫显性。
Eur J Immunol. 1995 Jul;25(7):1803-9. doi: 10.1002/eji.1830250702.
10
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.
引用本文的文献
1
Monoclonal Antibodies Against Myeloid Leukemia Cells: Current Knowledge and Future Directions.抗髓系白血病细胞的单克隆抗体：当前认知与未来方向。
Int J Mol Sci. 2025 May 10;26(10):4571. doi: 10.3390/ijms26104571.
2
Cancer therapy with antibodies.抗体癌症疗法。
Nat Rev Cancer. 2024 Jun;24(6):399-426. doi: 10.1038/s41568-024-00690-x. Epub 2024 May 13.
3
Plasticity of Amino Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A Viruses and Its Impact on Receptor Binding and Antibody Recognition.H3 猪流感病毒受体结合位点附近的氨基酸残基 145 的可塑性及其对受体结合和抗体识别的影响。
J Virol. 2019 Jan 4;93(2). doi: 10.1128/JVI.01413-18. Print 2019 Jan 15.
4
Mechanisms, manifestations, and failures of self-tolerance.自身耐受的机制、表现及失效
Immunol Res. 2003;27(2-3):161-8. doi: 10.1385/IR:27:2-3:161.
5
Virus-induced maturation and activation of autoreactive memory B cells.病毒诱导自身反应性记忆B细胞的成熟与激活。
J Exp Med. 2000 Dec 18;192(12):1763-74. doi: 10.1084/jem.192.12.1763.
6
B-cell responses to a peptide epitope: mutations in heavy chain alone lead to maturation of antibody responses.B细胞对肽表位的反应：仅重链中的突变导致抗体反应成熟。
Immunology. 1999 May;97(1):1-8. doi: 10.1046/j.1365-2567.1999.00743.x.
7
A recombinant Fab neutralizes dengue virus in vitro.一种重组Fab片段在体外可中和登革病毒。
J Biotechnol. 1999 Apr 15;69(2-3):183-90. doi: 10.1016/s0168-1656(99)00037-1.
8
Self-reactive B cells in nonautoimmune and autoimmune mice.非自身免疫和自身免疫小鼠中的自身反应性B细胞。
Immunol Res. 1998;17(1-2):49-61. doi: 10.1007/BF02786430.
9
Immune recognition of influenza hemagglutinin as a viral and a neo-self-antigen.流感血凝素作为病毒抗原和新自身抗原的免疫识别。
Immunol Res. 1998;17(1-2):23-32. doi: 10.1007/BF02786427.
10
Regulation of anti-double-stranded DNA B cells in nonautoimmune mice: localization to the T-B interface of the splenic follicle.非自身免疫小鼠中抗双链DNA B细胞的调节：定位于脾滤泡的T-B界面。
J Exp Med. 1997 Oct 20;186(8):1257-67. doi: 10.1084/jem.186.8.1257.
本文引用的文献
1
Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution.流感病毒血凝素膜糖蛋白在3埃分辨率下的结构
Nature. 1981 Jan 29;289(5796):366-73. doi: 10.1038/289366a0.
2
Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. I. Significant variation in repertoire expression between individual mice.BALB/c小鼠对流感病毒血凝素免疫反应中抗体多样性的产生。I. 个体小鼠之间 repertoire 表达的显著差异。
J Exp Med. 1983 Feb 1;157(2):687-704. doi: 10.1084/jem.157.2.687.
3
Immunoglobulin genes.免疫球蛋白基因
Annu Rev Immunol. 1983;1:499-528. doi: 10.1146/annurev.iy.01.040183.002435.
4
Structural basis of antibody function.抗体功能的结构基础。
Annu Rev Immunol. 1983;1:87-117. doi: 10.1146/annurev.iy.01.040183.000511.
5
Somatic generation of antibody diversity.抗体多样性的体细胞产生。
Nature. 1983 Apr 14;302(5909):575-81. doi: 10.1038/302575a0.
6
Three-dimensional structure of an antigenic mutant of the influenza virus haemagglutinin.流感病毒血凝素抗原突变体的三维结构
Nature. 1984;311(5987):678-80. doi: 10.1038/311678a0.
7
The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype).甲型流感病毒A/PR/8/34血凝素（H1亚型）的抗原结构。
Cell. 1982 Dec;31(2 Pt 1):417-27. doi: 10.1016/0092-8674(82)90135-0.
8
Molecular mechanisms of variation in influenza viruses.流感病毒变异的分子机制
Nature. 1982 Mar 11;296(5853):115-21. doi: 10.1038/296115a0.
9
Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies.用杂交瘤抗体确定的流感病毒血凝素的抗原结构
Nature. 1981 Apr 23;290(5808):713-7. doi: 10.1038/290713a0.
10
The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes.小鼠中的免疫球蛋白重链可变区（Igh-V）基因座。I. 一百个Igh-V基因构成七个同源基因家族。
Eur J Immunol. 1984 Oct;14(10):922-30. doi: 10.1002/eji.1830141012.
Zotero 插件