Functional capacities of clonal antibodies to Haemophilus influenzae type b polysaccharide.

Functional capacities of clonal antibodies to Haemophilus influenzae type b polysaccharide.
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b 型流感嗜血杆菌多糖克隆抗体的功能能力。

DOI:
10.1128/iai.63.8.2989-2994.1995
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发表时间:
1995
影响因子:
3.1
通讯作者:
Park,MK
Park,MK
中科院分区:
医学2区
文献类型:
--
作者:
Nahm,MH;Kim,KH;Anderson,P;Hetherington,SV;Park,MK

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B型流感嗜血杆菌(Hib)是一种重要的幼儿病原体,抗Hib多糖(PS)胶囊是一种线性的核糖基核糖醇磷酸聚合物,可以保护儿童。抗Hib-PS抗体的结构已经在分子水平上得到了很好的表征;大约三分之二的抗Hib-PS抗体使用一个命名为A2的V kappa基因,其余的抗Hib-PS抗体使用许多其他VL基因中的一个。为了了解这些抗体功能变异的结构基础,我们从成人制备了18个克隆性纯抗体,并研究了它们的亲和力、亲和力、体外杀菌效力以及降低新生大鼠菌血症的能力。亲和力和亲和力分别与短配体(3个重复单位)和长配体(20个重复单位)的浓度成反比,它们分别能与溶液中50%的抗Hib-PS抗体结合。新生大鼠的保护力与亲和力(r=0.02)和亲和力(r=0.16)之间没有显著的相关性。如预期的那样,体外杀灭50%细菌所需的抗体量与亲和力呈负相关(r=-0.32)。然而,高亲和力的抗体杀菌活性却出人意料地降低(r=0.38)。这表明亲和力可能比亲和力更能预测抗体功能。亲和力与亲和力呈负相关(r=0.0022.76,P=0.0 5),含有A2 V kappa基因产物的抗体亲和力较高(P<0.0 5),亲和力较低(P=0.0 6)。一种可能的解释是,含有A2基因的Abs的表位位于Hib-PS链本身内,而含有非A2基因的Abs的表位是Hib-PS的末端。
Haemophilus influenzae type b (Hib) is an important pathogen for young children, and children can be protected with antibodies (Abs) to Hib polysaccharide (PS) capsule, a linear polymer of ribosyl ribitol phosphate. The structure of anti-Hib-PS Abs has been well characterized at the molecular level; about two-thirds of anti-Hib-PS Abs use a V kappa gene named A2, and the remaining anti-Hib-PS Abs use one of many other VL genes. In order to understand the structural basis for the variability in the function of these Abs, we prepared 18 clonally pure Abs from adults and studied their affinity, avidity, bactericidal potency in vitro, and ability to reduce bacteremia in newborn rats. Affinities and avidities were determined as the inverse of the concentrations of short (3 repeating units) and long (20 repeating units) ligands which could bind 50% of anti-Hib-PS Ab in solution, respectively. No significant correlations between the protection of newborn rats and affinity (r = 0.02) or avidity (r = 0.16) were observed. The amount of Ab required to kill 50% of bacteria in vitro decreased with avidity (r = -0.32), as expected. However, Abs with high affinity were unexpectedly found to have less bactericidal activity (r = 0.38). This suggests that avidity may be a better predictor of Ab function than affinity. Affinity and avidity results were negatively correlated (r = 0.76, P = 0.0022), and Abs that had A2 V kappa gene products had higher avidity (P < 0.05) and lower affinity (P = 0.06) than Abs that had other VL genes. A possible explanation of these observations is that the epitope for Abs with the A2 gene is within the Hib-PS chain itself, whereas the epitope for Abs with a non-A2 gene is the terminus of Hib-PS.
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发表时间: 1991
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DOI: 10.1016/s0022-3476(89)80432-9
发表时间: 1989
期刊: The Journal of pediatrics
影响因子: --
作者:
Granoff,DM;Chacko,A;Lottenbach,KR;Sheetz,KE
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影响因子: 8
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DOI: --
发表时间: 1981
影响因子: 15.9
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