An idiotypic marker associated with a germ-line encoded kappa light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide.
An idiotypic marker associated with a germ-line encoded kappa light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide.
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一种与种系编码的 kappa 轻链可变区相关的独特型标记，该可变区在疫苗诱导的针对 b 型流感嗜血杆菌多糖的人抗体反应中占主导地位。
DOI：
10.1172/jci115502
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Scott,MG
中科院分区：
文献类型：
--
作者：
Lucas,AH;Langley,RJ;Granoff,DM;Nahm,MH;Kitamura,MY;Scott,MG
对 b 型流感嗜血杆菌多糖 (Hib PS) 具有特异性的人类抗体经常表达交叉反应独特型 (CRI)，并且通常利用 V kappa II 基因 A2 产物的 VL 区。为了进一步检查抗 Hib PS V 区表达并确定 CRI 表达是否与 V kappa IIA2 链相关，我们分离了与抗 Hib PS 抗体的独特型决定簇反应的单克隆抗体 (MAb)。该 MAb 抑制 Hib PS 结合，但不与 Ig 同种型决定簇发生反应。该 MAb 识别的 CRI（称为 HibId-1）与 Hib PS 结合位点相关，因为该 MAb 与抗 Hib PS 抗体的反应性可被 Hib PS 抑制。 HibId-1 由 17 个克隆纯化且序列确定的具有 V kappa IIA2 L 链的抗 Hib PS 抗体中的 17 个表达。相反，具有V lambda、V kappa I或V kappa III链的10个抗Hib PS抗体中有0个表达HibId-1。 Western blot 分析显示，MAb 抗 CRI 与分离的抗 Hib PS V kappa IIA2 L 链反应，但不与 H 链或其他 L 链反应，表明 HibId-1 决定簇定位于 V kappa IIA2 链，不需要与 H 链配对即可表达。携带 HibId-1 的抗 Hib PS 抗体存在于至少 85% 的用游离 Hib PS 或与白喉类毒素偶联的 Hib PS (Hib PS-DT) 免疫的受试者中，并且平均占总疫苗诱导血清抗 Hib PS 的 60%。 HibId-1 表达与疫苗接种年龄无关，因为婴儿、儿童和成人在接种 Hib PS-DT 后具有相似的 HibId-1 阳性抗 Hib PS 分布。与 Hib PS 免疫后血清相比，成人免疫前血清中 HibId-1 的表达频率较低，并且占总抗 Hib PS 抗体的比例较小，表明免疫优先刺激 HibId-1 阳性 B 细胞。这些数据表明，携带 HibId-1/V kappa IIA2 的抗体构成免疫诱导的抗 Hib PS 反应的主要成分，并且这种 VL 表达模式在个体发育早期就已建立。
Human antibodies specific for the Haemophilus influenzae b polysaccharide (Hib PS) frequently express a cross-reactive idiotype (CRI), and commonly utilize a VL region that is the product of the V kappa II gene A2. To examine further anti-Hib PS V region expression and to determine whether CRI expression is correlated with the V kappa IIA2 chain, we isolated a monoclonal antibody (MAb) reactive with an idiotypic determinant of anti-Hib PS antibodies. This MAb inhibited Hib PS binding but did not react with Ig isotypic determinants. The CRI recognized by this MAb, designated HibId-1, was associated with the Hib PS-combining site since the reactivity of the MAb with anti-Hib PS antibodies could be inhibited by Hib PS. HibId-1 was expressed by 17 of 17 clonally purified and sequence-defined anti-Hib PS antibodies having V kappa IIA2 L chains. In contrast, 0 of 10 anti-Hib PS antibodies having either V lambda, V kappa I, or V kappa III chains expressed HibId-1. Western blot analysis showed that the MAb anti-CRI reacted with isolated anti-Hib PS V kappa IIA2 L chains but not with H chains or other L chains, indicating that the HibId-1 determinant is localized to the V kappa IIA2 chain, and does not require pairing with H chain for expression. Anti-Hib PS antibodies bearing HibId-1 were present in at least 85% of subjects immunized with either free Hib PS or Hib PS coupled to diphtheria toxoid (Hib PS-DT), and comprised on the average 60% of the total vaccine-induced serum anti-Hib PS. HibId-1 expression was not related to age at vaccination inasmuch as infants, children, and adults had similar distributions of HibId-1-positive anti-Hib PS after vaccination with Hib PS-DT. HibId-1 was expressed at a lower frequency and comprised a smaller fraction of the total anti-Hib PS antibody in adult preimmunization sera as compared to post-Hib PS immunization sera, suggesting that immunization preferentially stimulates HibId-1-positive B cells. These data demonstrate that antibodies bearing HibId-1/V kappa IIA2 comprise a predominant component of the anti-Hib PS response induced by immunization, and that this pattern of VL expression is established early in ontogeny.Images