Autoantibody-defined epitopes on nuclear antigens are conserved, conformation-dependent and active site regions.
Autoantibody-defined epitopes on nuclear antigens are conserved, conformation-dependent and active site regions.
复制标题
DOI：
--
复制
发表时间：
1994-11
影响因子：
3.7
通讯作者：
Eng M. Tan;Yoshinao Muro;K. Pollard
中科院分区：
文献类型：
--
作者：
Eng M. Tan;Yoshinao Muro;K. Pollard
系统性风湿性疾病中的抗核抗体已成为鉴定核抗原和阐明驱动自身免疫反应的免疫机制的有力试剂。这些研究提出的概念包括：自身免疫反应是由抗原驱动的，自身抗原是亚细胞颗粒的组成部分，自身抗原参与重要的生物合成功能，自身抗体识别的表位是活性部位或功能结构域。增殖细胞核抗原是一种36 kDa的核蛋白，系统性红斑狼疮患者体内存在自身抗体。增殖细胞核抗原是DNA复制复合体的一个组成部分，与DNA聚合酶在复制分叉处的连续链DNA合成中有关。研究表明，狼疮抗体识别的增殖细胞核抗原表位具有构象依赖性。通过连接不连续的线性序列合成的复合肽用于免疫兔，其中一种复合肽诱导的抗体的性质与人类自身抗体惊人地相似。在全身性自身免疫性疾病中，免疫原可能是由蛋白质-蛋白质或蛋白质-核酸复合体组成的核内或其他细胞内颗粒，参与细胞生物合成功能。
Antinuclear antibodies in the systemic rheumatic diseases have been powerful reagents for identifying and characterizing nuclear antigens and for elucidating immune mechanisms which drive the autoimmune response. Concepts which have emerged from these studies include the following: the autoimmune response is antigen driven, autoantigens are components of subcellular particles, autoantigens are involved in important biosynthetic functions and epitopes recognized by autoantibodies are active sites or functional domain regions. PCNA (proliferating cell nuclear antigen) is a nuclear protein of 36 kDa and autoantibodies are present in patients with systemic lupus erythematosus. PCNA is a component of the DNA replication complex and is associated with DNA polymerase delta in continuous strand DNA synthesis at the replication fork. Studies have shown that epitopes on PCNA recognized by lupus antibodies are conformation-dependent. Composite peptides synthesized by joining discontinuous linear sequences were used to immunize rabbits and one such composite peptide induced antibodies with properties strikingly similar to human autoantibodies. Immunogens in the systemic autoimmune diseases are likely to be intranuclear or other intracellular particles composed of protein-protein or protein-nucleic acid complexes which are involved in cellular biosynthetic functions.