Brigido M M, Stollar B D
Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02159.
J Immunol. 1991 Mar 15;146(6):2005-9.
The cDNA for H and L chain V regions of two anti-Z-DNA mAb, Z22 and Z44, were cloned and sequenced. These are the first experimentally induced anti-nucleic acid antibody sequences available for comparison with autoantibody sequences. Z22 and Z44 are IgG2b and IgG2a antibodies from C57BL/6 mice. They recognize different facets of the Z-DNA structure. They both use VH10 family genes and share 95% sequence base sequence identity in the VH and leader sequences; however, they differ in the 5'-untranslated region of the VH mRNA, indicating they arise from different germline genes. Both use JH4 segments. They differ from each other very extensively in the CDR3 of both H and L chains. The most closely related H chains in the current GenBank/EMBL data base are two mouse IgG anti-DNA autoantibodies, one from an MRL-lpr/lpr mouse (MRL-DNA4) and one from an NZB/NZW mouse (BV04-01). Z22 and Z44 share 95% sequence identity with these antibodies in the VH segment. In addition, Z22 is identical to MRL-DNA4 at 91% of the positions in the 5'-untranslated region of the H chain mRNA. The two antibodies share 95% base sequence identity in the V kappa segment. The most closely related L chains, with 97 to 98% sequence identity, are the V kappa 10b germline gene for Z22 and the V kappa 10a germ line gene, which is associated with A/J anti-arsonate antibodies and BALB/c anti-ABO blood group substance antibodies, for Z44. Z22 and Z44 share several structural features (similarities in VH, JH, and V kappa) but differ very markedly in the L chain CDR1 and both H and L chain CDR3 sequences; these regions may determine the differences in their specific interactions with Z-DNA.
克隆并测序了两种抗Z-DNA单克隆抗体Z22和Z44的重链和轻链V区的cDNA。这些是首批可用于与自身抗体序列进行比较的经实验诱导产生的抗核酸抗体序列。Z22和Z44是来自C57BL/6小鼠的IgG2b和IgG2a抗体。它们识别Z-DNA结构的不同方面。它们都使用VH10家族基因，并且在VH和前导序列中具有95%的碱基序列同一性；然而，它们在VH mRNA的5'-非翻译区不同，表明它们起源于不同的种系基因。两者都使用JH4片段。它们在重链和轻链的CDR3中彼此差异非常大。当前GenBank/EMBL数据库中最密切相关的重链是两种小鼠IgG抗DNA自身抗体，一种来自MRL-lpr/lpr小鼠（MRL-DNA4），另一种来自NZB/NZW小鼠（BV04-01）。Z22和Z44在VH区段与这些抗体具有95%的序列同一性。此外，Z22在重链mRNA的5'-非翻译区91%的位置与MRL-DNA4相同。这两种抗体在Vκ区段具有95%的碱基序列同一性。最密切相关的轻链，具有97%至98%的序列同一性，对于Z22是Vκ10b种系基因，对于Z44是与A/J抗砷酸盐抗体和BALB/c抗ABO血型物质抗体相关的Vκ10a种系基因。Z22和Z44具有几个结构特征（VH、JH和Vκ中的相似性），但在轻链CDR1以及重链和轻链CDR3序列中差异非常明显；这些区域可能决定了它们与Z-DNA特异性相互作用的差异。
