DEVELOPMENT OF ANTIBODY REPERTOIRES TO POLYSACCHARIDES
多糖抗体库的开发
基本信息
- 批准号:6170031
- 负责人:
- 金额:$ 24.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-09-30 至 2002-08-31
- 项目状态:已结题
- 来源:
- 关键词:Haemophilus influenzae vaccines Streptococcus pneumoniae vaccine adult human (21+) age difference antibacterial antibody antibody specificity antigen antibody reaction bacterial polysaccharides clinical research developmental immunology enzyme linked immunosorbent assay flow cytometry genetic mapping genetic polymorphism human subject immunoconjugates immunoglobulin genes infant human (0-1 year) molecular cloning nucleic acid sequence polymerase chain reaction radioimmunoassay recombinant DNA
项目摘要
DESCRIPTION (Adapted from applicant's abstract): Antibody to bacterial
capsular polysaccharides are the major form of protection against infections
from pyogenic bacteria. The delay in ontogeny of human antibody responses
to polysaccharides predisposes the healthy infant to infection and defective
antibody responses renders patients with immunodeficiency, including the
aged and patients with AIDS or malnutrition, at high risk. The overall goal
of this proposal is to define the basis for the delayed ontogeny of human
antibody responses to polysaccharides. We have found that the dominant Vk
gene encoding high affinity human antibody to the Haemophilus influenzae b
capsular polysaccharides is the A2 gene, which maps to the Jk-distal region
of the locus, is used preferentially in germline form, and encodes antibody
when expressed with an arginine at the Vk-Jk junction that arises by N
region addition. We hypothesize that delayed rearrangement of critical Vk
genes that encode these highly restricted antibody repertoires and delayed
and infrequent N region addition contribute to this delay in ontogeny. This
proposal will address whether: 1) there is a delay in a) ontogeny of
immunoglobulin gene rearrangement of Vk genes located in the Jk-distal
region of the human Vk locus, and b) N region addition at the Vk-Jk
junction, which appears critical for the generation of an extended CDR3 loop
for binding of serum antibody to polysaccharides; 2) rearrangements of
Jk-distal Vk genes occur preferentially as secondary Vk-Jk rearrangements;
3) N region addition at Vk-Jk junctions occurs preferentially when L chain
rearrangement occurs at an early state of B cell development; 4) Vk gene
expression is affected by Ck light chain polymorphism; 5) pneumococcal
polysaccharides that induce antibody responses late in infancy are encoded b
map to the Jk-distal-region and require N region addition at their Vk-Jk
junction; 6) deletion of the N region-derived junctional CDR3 residue of
antibody to polysaccharides abolishes antibody binding. The results should
provide novel insights into the ontogeny of human antibody responses and
provide a background for developing vaccines that accelerate maturation of
antibody responses.
描述(改编自申请人摘要):细菌抗体
荚膜多糖是抵抗感染的主要形式
从化脓性细菌。 人类抗体应答的个体发育延迟
对多糖的依赖使健康的婴儿易于感染和缺陷
抗体反应使患者免疫缺陷,包括
老年人和艾滋病患者或营养不良者,高危。 总目标
这一建议的目的是确定人类延迟个体发育的基础,
对多糖的抗体反应。 我们发现,占主导地位的Vk
编码抗流感嗜血杆菌B的高亲和力人抗体的基因
荚膜多糖是A2基因,其定位于Jk远端区域
基因座,优先用于生殖系形式,并编码抗体
当在Vk-Jk连接处用精氨酸表达时,
区域添加。 我们假设临界Vk的延迟重排
编码这些高度限制性抗体库的基因,
和不频繁的N区添加有助于这种延迟的个体发育。 这
建议将解决以下问题:1)a)个体发育延迟
免疫球蛋白基因重排的Vk基因位于Jk-远端
B)在人Vk基因座的N区,和
连接,其对于产生延伸的CDR 3环似乎是关键的
用于血清抗体与多糖的结合; 2)
Jk-远端Vk基因优先发生次级Vk-Jk重排;
3)在Vk-Jk连接处的N区添加优先发生在L链
重排发生在B细胞发育的早期; 4)Vk基因
表达受Ck轻链多态性的影响; 5)肺炎球菌
在婴儿后期诱导抗体反应的多糖由B编码
映射到Jk远端区域,并需要在其Vk-Jk处添加N区域
6)缺失N区衍生的连接性CDR 3残基;
多糖的抗体消除抗体结合。 结果应
为人类抗体应答的个体发生提供了新的见解,
为开发疫苗提供了背景,
抗体反应。
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Bioeliminable nanohydrogels for drug delivery.
- DOI:10.1021/nl8017274
- 发表时间:2008-10
- 期刊:
- 影响因子:10.8
- 作者:Gao D;Xu H;Philbert MA;Kopelman R
- 通讯作者:Kopelman R
Inherent properties of somatic hypermutation as revealed by human non-productive VH6 immunoglobulin rearrangements.
人类非生产性 VH6 免疫球蛋白重排揭示了体细胞超突变的固有特性。
- DOI:10.1046/j.1365-2567.1998.00427.x
- 发表时间:1998
- 期刊:
- 影响因子:6.4
- 作者:Varade,WS;Carnahan,JA;Kingsley,PD;Insel,RA
- 通讯作者:Insel,RA
Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat.
大鼠静脉注射后稳定的聚丙烯酰胺纳米颗粒的组织分布和药代动力学。
- DOI:10.1016/j.taap.2010.11.017
- 发表时间:2011-03-15
- 期刊:
- 影响因子:3.8
- 作者:Wenger Y;Schneider RJ 2nd;Reddy GR;Kopelman R;Jolliet O;Philbert MA
- 通讯作者:Philbert MA
Characteristics of somatic hypermutation of human immunoglobulin genes.
人免疫球蛋白基因体细胞超突变的特征。
- DOI:10.1007/978-3-642-71984-4_4
- 发表时间:1998
- 期刊:
- 影响因子:0
- 作者:Insel,RA;Varade,WS
- 通讯作者:Varade,WS
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Richard A. Insel其他文献
50812 Infant Skin Microbiome is Associated with Decreased Risk of Atopic Dermatitis and Affected by Early Use of an Emollient
- DOI:
10.1016/j.jaad.2024.07.226 - 发表时间:
2024-09-01 - 期刊:
- 影响因子:
- 作者:
Richard A. Insel;Jonathan O’B. Hourihane;Albert Palleja;Janne Marie Moll;Nikolaj Sørensen;Alan D. Irvine;Georgios Stamatas - 通讯作者:
Georgios Stamatas
Anticorps monoclonaux humains contre des toxines bactériennes
人类单克隆抗体对抗细菌毒素
- DOI:
- 发表时间:
1983 - 期刊:
- 影响因子:0
- 作者:
Richard A. Insel;Francis Gigliotti - 通讯作者:
Francis Gigliotti
Alterations of T helper/inducer and T suppressor/inducer cells in patients with recurrent aphthous ulcers.
复发性阿弗他溃疡患者 T 辅助细胞/诱导细胞和 T 抑制细胞/诱导细胞的改变。
- DOI:
10.1016/0030-4220(90)90329-q - 发表时间:
1990 - 期刊:
- 影响因子:0
- 作者:
Regina Landesberg;Margaret Fallon;Richard A. Insel - 通讯作者:
Richard A. Insel
The necessity for T cell help for human tonsil B cell responses to pokeweed mitogens: induction of DNA synthesis, immunoglobulin, and specific antibody production with a T cell helper factor produced with pokeweed mitogen.
T 细胞帮助人扁桃体 B 细胞对商陆有丝分裂原作出反应的必要性:诱导 DNA 合成、免疫球蛋白以及用商陆有丝分裂原产生的 T 细胞辅助因子产生特异性抗体。
- DOI:
10.4049/jimmunol.118.6.2009 - 发表时间:
1977 - 期刊:
- 影响因子:4.4
- 作者:
Richard A. Insel;Ezio Merler - 通讯作者:
Ezio Merler
Richard A. Insel的其他文献
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{{ truncateString('Richard A. Insel', 18)}}的其他基金
ONTOGENY OF GENERATION OF NEONATAL ANTIBODY DIVERSITY
新生儿抗体多样性产生的个体发生
- 批准号:
6182444 - 财政年份:1997
- 资助金额:
$ 24.25万 - 项目类别:
ONTOGENY OF GENERATION OF NEONATAL ANTIBODY DIVERSITY
新生儿抗体多样性产生的个体发生
- 批准号:
2593018 - 财政年份:1997
- 资助金额:
$ 24.25万 - 项目类别:
ONTOGENY OF GENERATION OF NEONATAL ANTIBODY DIVERSITY
新生儿抗体多样性产生的个体发生
- 批准号:
2674152 - 财政年份:1997
- 资助金额:
$ 24.25万 - 项目类别:
ONTOGENY OF GENERATION OF NEONATAL ANTIBODY DIVERSITY
新生儿抗体多样性产生的个体发生
- 批准号:
2889485 - 财政年份:1997
- 资助金额:
$ 24.25万 - 项目类别:
DEVELOPMENT OF ANTIBODY REPERTOIRES TO POLYSACCHARIDES
多糖抗体库的开发
- 批准号:
2073742 - 财政年份:1994
- 资助金额:
$ 24.25万 - 项目类别:
DEVELOPMENT OF ANTIBODY REPERTOIRES TO POLYSACCHARIDES
多糖抗体库的开发
- 批准号:
2073744 - 财政年份:1994
- 资助金额:
$ 24.25万 - 项目类别:
DEVELOPMENT OF ANTIBODY REPERTOIRES TO POLYSACCHARIDES
多糖抗体库的开发
- 批准号:
2886973 - 财政年份:1994
- 资助金额:
$ 24.25万 - 项目类别:
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