V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice.
V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice.
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NZB/NZW F1 小鼠的抗 DNA 和抗 RNA 自身抗体的 V 区序列。
DOI：
10.4049/jimmunol.141.5.1745
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发表时间：
1988
影响因子：
4.4
通讯作者：
Anthony R. Rees
中科院分区：
文献类型：
--
作者：
D. Eilat;David M. Webster;Anthony R. Rees
通过 mRNA 测序确定源自狼疮倾向 NZB/NZW F1 雌性小鼠的两种抗 DNA（A52、D42）和两种抗 RNA（D44、D444）自身抗体的 V 区序列。该序列具有以下特点：1）抗DNA和抗RNA抗体之间没有明确的序列关系； 2)任何L链序列之间不存在重大相似性，并且每个VL基因片段属于不同的小鼠VK亚组； 3) 两种抗RNA抗体的H链显示出密切相关的VH基因片段序列和非常相似的第三互补决定区（CDR3）； 4)两种抗DNA抗体的H链具有属于不同VH基因家族的VH片段，但具有独特且相似的D片段和连接序列组合，表明H链CDR3中存在Ag和/或独特型调节的共同识别元件； 5)发现一种抗DNA抗体(D42)的VH基因片段与结合环境Ag磷酸胆碱的CBA小鼠杂交瘤抗体(6G6)的VH基因片段非常相似。抗DNA抗体(D42)的Fv区的三维结构通过计算机建模，并将一段聚(dT)、单链DNA对接至抗体结合位点的裂口，由三个H链CDR和L链的CDR1和CDR3形成。该裂口的特征是精氨酸和酪氨酸残基占优势，排列在裂口壁和基底上。
The V region sequences of two anti-DNA (A52, D42) and two anti-RNA (D44, D444) autoantibodies, derived from lupus prone NZB/NZW F1 female mice, were determined by mRNA sequencing. The sequences had the following features: 1) there was no clear sequence relationship between anti-DNA and anti-RNA antibodies; 2) there were no major similarities between any of the L chain sequences and each VL gene segment belonged to a different mouse VK subgroup; 3) the H chains of the two anti-RNA antibodies showed closely related sequences of VH gene segments and very similar third complementarity determining regions (CDR3); 4) the H chains of the two anti-DNA antibodies had VH segments belonging to different VH gene families but had a unique and similar combination of D segments and junctional sequences, suggesting a common recognition element for Ag and/or for idiotypic regulation in the H chain CDR3; and 5) the VH gene segment of one anti-DNA antibody (D42) was found to be very similar to the VH gene segment of a CBA mouse hybridoma antibody (6G6) which binds to the environmental Ag phosphocholine. The three-dimensional structure of the Fv-region of the anti-DNA antibody (D42) was modeled by computer and a stretch of poly(dT), ssDNA was docked to a cleft in the antibody combining site, formed by the three H chain CDR and by CDR1 and CDR3 of the L chain. The cleft is characterized by a preponderance of arginine and tyrosine residues, lining both the walls and base of the cleft.