COMPARISON OF PATHOGENIC AND NONPATHOGENIC MURINE ANTIBODIES TO DNA - ANTIGEN-BINDING AND STRUCTURAL CHARACTERISTICS
COMPARISON OF PATHOGENIC AND NONPATHOGENIC MURINE ANTIBODIES TO DNA - ANTIGEN-BINDING AND STRUCTURAL CHARACTERISTICS
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DOI：
10.1093/intimm/6.6.817
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发表时间：
1994-06-01
影响因子：
4.4
通讯作者：
TSAO, BP
中科院分区：
文献类型：
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作者：
OHNISHI, K;EBLING, FM;TSAO, BP
比较了3株致病性和2株非致病性NZB/NZW F1单抗对DNA的影响。致病性定义为诱导BALB/c小鼠肾炎的能力。所有单抗均为IgG2a或2b，对双链DNA亲和力高，补体结合良好。三种病原菌均表达IdGN2独特型。接受致病性单抗的小鼠(与非致病性单抗相比)有更多的肾小球免疫球蛋白沉积。这两种病原体的独特性质是：Hep-2核染色均匀，能与(I)核小体、(Ii)组蛋白(mAb与DNA络合后)、(Iii)肾基膜上的硫酸乙酰肝素(与DNA/组蛋白络合后)和(Iv)体内细胞核结合。对重链和轻链V区核苷酸和氨基酸序列的比较表明，存在多个V(H)DJ(H)和V(Chi)J(Chi)基因家族，其他人也描述了几个抗DNA‘家族’。所有病原体V(H)链的CDR2或CDR3中均含有精氨酸(R)，非病原体V(H)链的CDR中不存在R。病原菌V(H)CDR中正负电荷AA较非病原菌多见。我们推测，与非病原体相比，V(H)CDR区决定的单抗的三级结构允许与病原体中带负电荷的抗原(DNA和硫酸乙酰肝素)和带正电荷的分子(组蛋白)有更强的结合。
Three pathogenic and two non-pathogenic NZB/NZW F1 mAbs to DNA were compared. Pathogenicity was defined as the ability to induce nephritis in BALB/c mice. All mAbs were IgG2a or 2b, had high avidity for double-stranded DNA and fixed complement well. All three pathogens expressed idiotype IdGN2. Mice receiving pathogenic mAbs (compared with non-pathogenic) had more glomerular IgG deposits. The unique properties of two of the pathogens were: strong homogeneous staining of Hep-2 nuclei and the ability to bind (i) nucleosomes, (ii) histone (after mAb complexed with DNA), (iii) heparan sulfate in renal basement membranes (after complexing with DNA/histone) and (iv) nuclei in vivo. Comparison of nucleotide and amino acid sequences of the V regions of heavy and light Ig chains showed use of multiple V(H)DJ(H) and V(chi)J(chi) gene families, with representation of several anti-DNA 'families' described by others. Arginine (R) occurred in the CDR2 or CDR3 of V(H) chains in all pathogens; R was absent in the CDRs of V(H) chains of non-pathogens. Positively and negatively charged AA were more frequent in V(H) CDR of pathogens than of non-pathogens. We hypothesize that the tertiary structure of mAbs determined by V(H) CDR regions permits stronger binding to negatively charged antigens (DNA and heparan sulfate) and to positively charged molecules (histone) in pathogens compared with non-pathogens.