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核糖核蛋白(RNP)抗体自身免疫抗原决定簇的特征分析。

Characterization of the autoimmune antigenic determinant for ribonucleoprotein (RNP) antibody.

作者信息

Agris P F, KiKuchi Y, Gross H J, Takano M, Sharp G C

出版信息

Immunol Commun. 1984;13(2):137-49. doi: 10.3109/08820138409025457.

DOI:10.3109/08820138409025457
PMID:6204927
Abstract

Small nuclear ribonucleoprotein complexes are antigens in various autoimmune diseases. The serological pattern of high titers of circulating antibody to nuclear ribonucleoprotein (RNP) antigen is a diagnostic marker for mixed connective tissue disease (MCTD); whereas antibody to Sm is prevalent in systemic lupus erythematosus (SLE). Both calf thymus and rabbit thymus are commonly used, excellent sources for preparation of the corresponding antigens RNP and Sm in clinical and research laboratories (A. M. Boak et al., accompanying paper). Thus, biochemical and structural characterization of the minimal antigenic determinant in these preparations is important for its use in the laboratory, as well as significant for understanding MCTD, SLE, and other examples of autoimmunity. Purification and biochemical analyses of immunologically active RNP from many different preparations of calf thymus extract has revealed that the majority of antibody in monospecific MCTD patient sera recognizes an antigen composed of the 165 nucleotide RNA, U1 RNA, and five peptides. Calf thymus U1 RNA was found to be identical in sequence to that of man. A sequence of 55 nucleotides within the 165 nucleotide RNA was the minimal RNA fragment found in RNP particles that were still immunologically active. Two of the RNP peptides react with patient sera monospecific for RNP and thus, are presumably the antigenic peptides complexed with the 55 nucleotide RNA sequence.

摘要

小核核糖核蛋白复合体是多种自身免疫性疾病中的抗原。针对核糖核蛋白(RNP)抗原的循环抗体高滴度血清学模式是混合性结缔组织病(MCTD)的诊断标志物;而抗Sm抗体在系统性红斑狼疮(SLE)中较为常见。小牛胸腺和兔胸腺都是临床和研究实验室中常用的、制备相应抗原RNP和Sm的优质来源(A.M.博克等人,附文)。因此,对这些制剂中最小抗原决定簇进行生化和结构表征,对于其实验室应用很重要,对于理解MCTD、SLE及其他自身免疫性疾病实例也意义重大。对来自多种不同小牛胸腺提取物制剂的具有免疫活性的RNP进行纯化和生化分析后发现,单特异性MCTD患者血清中的大多数抗体识别的抗原由165个核苷酸的RNA、U1 RNA和五种肽组成。发现小牛胸腺U1 RNA的序列与人的相同。165个核苷酸RNA中的一段55个核苷酸的序列是在仍具有免疫活性的RNP颗粒中发现的最小RNA片段。两种RNP肽与对RNP单特异性的患者血清发生反应,因此,推测它们是与55个核苷酸RNA序列复合的抗原肽。

相似文献

1
Characterization of the autoimmune antigenic determinant for ribonucleoprotein (RNP) antibody.核糖核蛋白(RNP)抗体自身免疫抗原决定簇的特征分析。
Immunol Commun. 1984;13(2):137-49. doi: 10.3109/08820138409025457.
2
Autoantibodies reactive with small ribonucleoprotein antigens: a convergence of molecular biology and clinical immunology.与小核糖核蛋白抗原反应的自身抗体:分子生物学与临床免疫学的交汇点
J Clin Lab Immunol. 1984 Sep;15(1):1-17.
3
Immunization of mice with purified U1 small nuclear ribonucleoprotein (RNP) induces a pattern of antibody specificities characteristic of the anti-Sm and anti-RNP autoimmune response of patients with lupus erythematosus, as measured by monoclonal antibodies.用纯化的U1小核核糖核蛋白(RNP)免疫小鼠,通过单克隆抗体检测发现,诱导出了红斑狼疮患者抗Sm和抗RNP自身免疫反应所特有的抗体特异性模式。
Proc Natl Acad Sci U S A. 1986 Nov;83(22):8689-93. doi: 10.1073/pnas.83.22.8689.
4
The purification, characterization and amino acid analysis of nuclear ribonuclear protein and Sm antigens reacting with human autoimmune sera.与人类自身免疫血清发生反应的核糖核蛋白和Sm抗原的纯化、特性鉴定及氨基酸分析。
Clin Invest Med. 1983;6(2):61-71.
5
Further characterization and subcellular localization of Sm and U1 ribonucleoprotein antigens.Sm和U1核糖核蛋白抗原的进一步特性鉴定及亚细胞定位
Eur J Immunol. 1985 Oct;15(10):992-7. doi: 10.1002/eji.1830151006.
6
Characterization of antigenic polypeptides of the RNP, Sm and SS-B nuclear antigens from calf thymus.
Mol Immunol. 1984 Aug;21(8):731-9. doi: 10.1016/0161-5890(84)90026-9.
7
Mapping of epitopes on U1 snRNP polypeptide A with synthetic peptides and autoimmune sera.利用合成肽和自身免疫血清对U1 snRNP A多肽上的表位进行定位
Clin Exp Immunol. 1991 Oct;86(1):71-8. doi: 10.1111/j.1365-2249.1991.tb05776.x.
8
Antibodies from patients with mixed connective tissue disease react with heterogeneous nuclear ribonucleoprotein or ribonucleic acid (hnRNP/RNA) of the nuclear matrix.混合性结缔组织病患者的抗体与核基质的不均一核糖核蛋白或核糖核酸(hnRNP/RNA)发生反应。
J Immunol. 1984 Mar;132(3):1216-22.
9
Small nuclear ribonucleoprotein antigens are absent from 10S translation inhibitory ribonucleoprotein but present in cytoplasmic messenger ribonucleoprotein and polysomes.小核核糖核蛋白抗原不存在于10S翻译抑制核糖核蛋白中,但存在于细胞质信使核糖核蛋白和多核糖体中。
Arch Biochem Biophys. 1986 Jul;248(1):89-100. doi: 10.1016/0003-9861(86)90404-2.
10
The structure of mammalian small nuclear ribonucleoproteins. Identification of multiple protein components reactive with anti-(U1)ribonucleoprotein and anti-Sm autoantibodies.哺乳动物小核核糖核蛋白的结构。与抗(U1)核糖核蛋白和抗Sm自身抗体反应的多种蛋白质成分的鉴定。
J Biol Chem. 1984 May 10;259(9):5907-14.

引用本文的文献

1
Intranuclear localization of snRNP antigens.小核核糖核蛋白抗原的核内定位。
J Cell Biol. 1986 Jan;102(1):137-44. doi: 10.1083/jcb.102.1.137.
2
U1 small nuclear ribonucleoprotein particle-specific proteins interact with the first and second stem-loops of U1 RNA, with the A protein binding directly to the RNA independently of the 70K and Sm proteins.U1小核核糖核蛋白颗粒特异性蛋白与U1 RNA的第一和第二个茎环相互作用,其中A蛋白独立于70K和Sm蛋白直接与RNA结合。
Mol Cell Biol. 1989 Aug;9(8):3360-8. doi: 10.1128/mcb.9.8.3360-3368.1989.
3
U1 SnRNP association with HnRNP involves an initial non-specific splice-site independent interaction of U1 SnRNP protein with HnRNA.
U1 小核核糖核蛋白颗粒(SnRNP)与不均一核糖核蛋白(HnRNP)的结合涉及 U1 SnRNP 蛋白与核内不均一核糖核酸(HnRNA)最初的非特异性、不依赖剪接位点的相互作用。
Mol Cell Biochem. 1991 Jul 24;106(1):55-66. doi: 10.1007/BF00231189.