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在La/SS-B自身抗原保守区域中鉴定出一种人类特异性表位。

Identification of a human-specific epitope in a conserved region of the La/SS-B autoantigen.

作者信息

Weng Y M, McNeilage J, Topfer F, McCluskey J, Gordon T

机构信息

Department of Clinical Immunology, Flinders Medical Centre, Bedford Park, South Australia.

出版信息

J Clin Invest. 1993 Aug;92(2):1104-8. doi: 10.1172/JCI116617.

DOI:10.1172/JCI116617
PMID:7688758
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC294953/
Abstract

Human anti-La/SS-B autoantibodies are known to react with highly conserved epitopes suggested to be functional or active sites on the La/SS-B polypeptide. This study was designed to determine whether the autoantibodies also react with poorly conserved regions of La/SS-B as predicted by an antigen-driven autoimmune response. Binding of human autoantibodies to purified human, mouse, and bovine recombinant fragments representing immunodominant regions of the La/SS-B polypeptide was compared using Western blotting and ELISA. A cross-reactive epitope was located in the highly conserved NH2-terminal region of La/SS-B. Significantly, human-specific epitopes were identified in both the conserved RNA-recognition motif and a poorly conserved COOH-terminal fragment, providing direct evidence for an autoantigen-driven response. The lack of autoantibody cross-reactivity with a conserved domain of mouse and bovine La/SS-B implies that a small number of residues in human autoepitopes may be critical for autoimmunogenicity.

摘要

已知人类抗La/SS - B自身抗体可与高度保守的表位发生反应，这些表位被认为是La/SS - B多肽上的功能或活性位点。本研究旨在确定这些自身抗体是否也会与抗原驱动的自身免疫反应所预测的La/SS - B的低保守区域发生反应。使用蛋白质印迹法和酶联免疫吸附测定法比较了人类自身抗体与代表La/SS - B多肽免疫显性区域的纯化人、小鼠和牛重组片段的结合情况。一个交叉反应表位位于La/SS - B高度保守的NH2末端区域。值得注意的是，在保守的RNA识别基序和一个低保守的COOH末端片段中均鉴定出了人类特异性表位，这为自身抗原驱动的反应提供了直接证据。人类自身抗体与小鼠和牛La/SS - B的保守结构域缺乏交叉反应性，这意味着人类自身表位中的少数残基可能对自身免疫原性至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/afdd434288e3/jcinvest00029-0580-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/3ad29839990e/jcinvest00029-0579-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/a15031cac3cb/jcinvest00029-0580-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/f266e98956ce/jcinvest00029-0580-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/dc73c7c4a490/jcinvest00029-0580-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/afdd434288e3/jcinvest00029-0580-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/3ad29839990e/jcinvest00029-0579-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/a15031cac3cb/jcinvest00029-0580-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/f266e98956ce/jcinvest00029-0580-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/dc73c7c4a490/jcinvest00029-0580-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a5/294953/afdd434288e3/jcinvest00029-0580-d.jpg

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Purified lupus antigen La recognizes an oligouridylate stretch common to the 3' termini of RNA polymerase III transcripts.纯化的狼疮抗原La识别RNA聚合酶III转录本3'末端共有的一段寡聚尿苷酸序列。
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The lupus autoantigens and the pathogenesis of systemic lupus erythematosus.
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Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):875-9. doi: 10.1073/pnas.92.3.875.
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