Monestier M, Fasy T M, Debbas M E, Bohm L
Institute of Molecular Immunology, University of Medicine and Dentistry of New Jersey, Newark.
Clin Exp Immunol. 1990 Jul;81(1):39-44. doi: 10.1111/j.1365-2249.1990.tb05288.x.
Autoantibodies to histone H1 represent the most common specificity among anti-histone autoantibodies in systemic autoimmune diseases. Here we analyse anti-H1 autoantibodies in mice from the following autoimmune strains: MRL/Mp-lpr/lpr, NZB and NZB x NZW/F1. Autoantibodies of the IgM isotype bind predominantly to epitopes located in the COOH-terminal domain of the H1 molecule, whereas IgG autoantibodies in the MRL/Mp-lpr/lpr and NZB strains also recognize epitopes requiring the integrity of both the COOH-terminal and the central globular domains of H1. In both of these strains, the titre of these IgG anti-H1 antibodies rises during the course of the disease. The importance of three-dimensional structure of histone H1 was attested by a significant decrease in IgG binding after cleavage of the H1 molecule within the folded globular domain. The binding of these sera to H1 variants from various species was also investigated and a strong binding of MRL/Mp-lpr/lpr sera to certain phylogenetically distant histone H1 variant molecules (sea-urchin sperm H1 and chicken erythrocyte H5) was observed. This cross-reacting binding can be explained by the presence in MRL/Mp-lpr/lpr sera of autoantibodies to H1(0), a variant found in non-dividing cells and exhibiting sequence homologies to the above mentioned variants. The significance and the possible implications of these data for the pathogenesis of autoimmunity are discussed.
在系统性自身免疫性疾病中，组蛋白H1自身抗体是抗组蛋白自身抗体中最常见的特异性类型。在此，我们分析了来自以下自身免疫品系小鼠的抗H1自身抗体：MRL/Mp-lpr/lpr、NZB和NZB×NZW/F1。IgM同种型自身抗体主要结合位于H1分子COOH末端结构域的表位，而MRL/Mp-lpr/lpr和NZB品系中的IgG自身抗体也识别需要H1的COOH末端和中央球状结构域均完整的表位。在这两个品系中，这些IgG抗H1抗体的滴度在疾病过程中都会升高。通过在折叠球状结构域内切割H1分子后IgG结合显著减少，证明了组蛋白H1三维结构的重要性。还研究了这些血清与来自不同物种的H1变体的结合情况，观察到MRL/Mp-lpr/lpr血清与某些系统发育上较远的组蛋白H1变体分子（海胆精子H1和鸡红细胞H5）有强烈结合。这种交叉反应性结合可以用MRL/Mp-lpr/lpr血清中存在针对H1(0)的自身抗体来解释，H1(0)是一种在非分裂细胞中发现的变体，与上述变体具有序列同源性。讨论了这些数据对自身免疫发病机制的意义和可能影响。
