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La/SS - B核糖核蛋白自身抗原NH2末端不连续免疫显性表位的定义。

Definition of a discontinuous immunodominant epitope at the NH2 terminus of the La/SS-B ribonucleoprotein autoantigen.

作者信息

McNeilage L J, Umapathysivam K, Macmillan E, Guidolin A, Whittingham S, Gordon T

机构信息

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

出版信息

J Clin Invest. 1992 May;89(5):1652-6. doi: 10.1172/JCI115762.

DOI:10.1172/JCI115762
PMID:1373741
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC443042/
Abstract

High-titer IgG autoantibodies to the La/SS-B ribonucleoprotein (RNP) are a hallmark of patients with primary Sjogren's syndrome. Anti-La/SS-B-positive human sera bind to multiple epitopes on recombinant La/SS-B, although the initial response is against an immunodominant epitope within the first 107 NH2-terminal amino acids (aa). Sequence analysis has identified a striking homology between aa 88-101 in this NH2-terminal region of La/SS-B and a feline retroviral gag polypeptide suggesting the anti-La/SS-B response may be initiated by cross-reactivity with an exogenous agent. In the present study, detailed mapping of this NH2-terminal epitope, using recombinant La/SS-B purified from the expression of overlapping DNA fragments spanning aa 1-107, has shown that this immunodominant epitope is a complex conformational or discontinuous epitope dependent upon both aa 12-28 and 82-99 for expression, even though these regions share no homology with each other. This requirement questions the significance of the homology between La/SS-B and a retroviral gag polypeptide in the generation of the B cell response to La/SS-B and is in accord with the general concept that B cells recognize conformational epitopes on antigens rather than small linear peptide sequences. The finding also reinforces the notion that native autoantigen could be the initiator of the autoimmune response.

摘要

针对La/SS - B核糖核蛋白（RNP）的高效价IgG自身抗体是原发性干燥综合征患者的一个标志。抗La/SS - B阳性的人血清与重组La/SS - B上的多个表位结合，尽管最初的反应是针对前107个氨基末端氨基酸（aa）内的一个免疫显性表位。序列分析已确定在La/SS - B的这个氨基末端区域中88 - 101位氨基酸与一种猫逆转录病毒gag多肽之间存在显著同源性，这表明抗La/SS - B反应可能是由与一种外源性因子的交叉反应引发的。在本研究中，利用从跨越1 - 107位氨基酸的重叠DNA片段表达中纯化得到的重组La/SS - B对这个氨基末端表位进行详细定位，结果表明这个免疫显性表位是一个复杂的构象性或不连续表位，其表达依赖于12 - 28位和82 - 99位氨基酸，尽管这些区域彼此之间没有同源性。这一需求对La/SS - B与逆转录病毒gag多肽之间的同源性在产生针对La/SS - B的B细胞反应中的意义提出了质疑，并且与B细胞识别抗原上的构象性表位而非小线性肽序列的一般概念相符。这一发现还强化了天然自身抗原可能是自身免疫反应引发者的观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/443042/be49daf434ae/jcinvest00049-0296-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/443042/dc56549450fb/jcinvest00049-0295-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/443042/cbe473dcfdcf/jcinvest00049-0296-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/443042/be49daf434ae/jcinvest00049-0296-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/443042/dc56549450fb/jcinvest00049-0295-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/443042/cbe473dcfdcf/jcinvest00049-0296-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad21/443042/be49daf434ae/jcinvest00049-0296-b.jpg

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