Molecular localization of human IgG anti-F(ab')2 reactivity with variable- and constant-region lambda light-chain epitopes.
Molecular localization of human IgG anti-F(ab')2 reactivity with variable- and constant-region lambda light-chain epitopes.
复制标题
人 IgG 抗 F(ab)2 与可变区和恒定区 lambda 轻链表位反应性的分子定位。
DOI：
10.1007/bf01541325
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发表时间：
1995
影响因子：
9.1
通讯作者：
Solomon,A
中科院分区：
文献类型：
--
作者：
WilliamsJr,RC;Malone,CC;Silvestris,F;Solomon,A
人IgG抗体与F（ab’）2片段上的抗原决定因子反应，代表存在于正常人血清中的通用抗独特型抗体。此外，系统性红斑狼疮（SLE）患者血清中这些抗体的滴度与疾病活动性呈负相关。由于这些自身抗体主要识别轻链相关的表位，特别是λ型，我们在聚丙烯针上合成了恒定(C)λ和可变(V)λ相关的重叠7-mer肽，以确定人类λ轻链上的抗f （ab’）2反应性表位。利用人λ轻链序列重叠7-mers检测正常人和SLE患者亲和纯化的抗f （ab’）2抗体，以及针对c λ和v λ亚群相关决定因子的小鼠抗人轻链单克隆抗体的ELISA反应性。正常和slee来源的抗f （ab’）2抗体对c - λ相关肽的反应模式相似。然而，正常和slel相关的抗f （ab’）2自身抗体对v λ相关肽的反应性谱明显不同。SLE IgG抗f （ab’）2抗体的反应性下降是由于特定的氨基酸v λ互补决定区（CDR）残基，包括27和54位的甘氨酸，16和37位的丙氨酸，28和91位的酪氨酸。这种与正常反应性不同的模式可能表明SLE中存在抗独特型控制机制的失败，这反映在免疫优势VλCDR残基的抗体产生缺陷上。
Human IgG antibodies reacting with antigenic determinants on F(ab′)2fragments represent generic antiidiotypic antibodies present in the serum of normal individuals. Additionally, the titers of these antibodies in the sera of patients with systemic lupus erythematosus (SLE) are inversely related to disease activity. Because these autoantibodies recognize predominantly light chain-related epitopes, especially λ type, we synthesized constant (C)λ- and variable (V)λ-related overlapping 7-mer peptides on polypropylene pins to determine anti-F(ab′)2-reactive epitopes on humanλlight chains. ELISA reactivity of affinity-purified anti-F(ab′)2antibodies obtained from normal individuals and from patients with SLE, as well as murine anti-human light-chain monoclonal antibodies specific for Cλand Vλsubgroup-related determinants, was tested using the overlapping 7-mers of humanλlight-chain sequence. The patterns of reactivity against Cλ-related peptides were similar in both normal and SLE-derived anti-F(ab′)2antibodies. However, reactivity profiles against Vλ-related peptides were distinctively different between the normal and the SLE-associated anti-F(ab′)2autoantibodies. A decrease in reactivity among the SLE IgG anti-F(ab′)2antibodies was noted for particular amino acid Vλcomplementarity-determining region (CDR) residues, including glycine at positions 27 and 54, alanine at 16 and 37, and tyrosine at 28 and 91. This different pattern of reactivity from normal may indicate that in SLE there is a failure of antiidiotypic control mechanisms, as reflected by a defect in production of antibody to immunodominant VλCDR residues.