Expressing a novel class of heavy chain antibodies
Expressing a novel class of heavy chain antibodies
批准号:
10555257
负责人:
ELLEN HSU
金额:
$24.23万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-01-25 至 2024-12-31
关键词:
Amino AcidsAntibodiesAntibody RepertoireAntigensArginineBacterial AntigensBacterial CapsulesBindingBinding SitesBypassCell WallChargeChondrichthyesComplementary DNACoupledDiseaseEpitopesEventExonsFishesFutureGenesHaptensHumanImmune responseImmunoglobulinsImmunotherapyInfectionLigand BindingLigandsLightLlamaLysineMicrobeMolecularMonoclonal AntibodiesMormyridaeMouse Cell LineMutant Strains MiceProteinsReading FramesReagentReportingRoleSharkStreptococcus pneumoniaeSurfaceTestingTransgenesTransgenic MiceV(D)J RecombinationVertebratesantibody detectionantigen bindingdrug developmentexperimental studyflexibilitynovelpathogenpolypeptidetool
中文摘要
项目摘要
重链抗体(HCAbs)是骆驼科动物表达的一种罕见的免疫球蛋白
还有鲨鱼它们以同源二聚体形式存在,其中每个多肽的可变(V)结构域结合配体。
不需要常规抗体中的轻链配偶体,HCAb试剂具有
尺寸和分子可操作性的优势,并且是药物开发的有前途的工具,
免疫疗法
编码HCAbs的基因在软骨鱼的两个亚类中分别进化,
百万年前他们的HCAbs和病原体识别能力的作用还没有被证实。
表征,尽管已经确定HCAb凸抗原结合位点可以检测
表位不能被常规抗体接近或绕过。我们已经发现了新的抗体基因,
一种软骨鱼,其组成基因片段已经进化到编码并重新排列以表达
在配体结合位点的赖氨酸和赖氨酸。一种抗体库,其主要抗原结合
环是灵活的,并且是脊椎动物中唯一的正电性,这为寻找抗原提供了机会。
与传统定义不同的决定因素。
将产生转基因小鼠以表达一组嵌合鱼基因。第一个目标是
第一个建议是产生突变小鼠,第二个是测试转基因库的能力,
对各种免疫原有反应。提出实验来测试HCAb检测中的新表位。
细菌荚膜和细胞壁。未来的研究将确定它们对疾病的保护作用。
英文摘要
PROJECT SUMMARY
Heavy chain antibodies (HCAbs) are an unusual species of immunoglobulins expressed by camelids
and sharks. They occur as homodimers in which the variable (V) domain of each polypeptide binds ligand.
Without the requirement for the light chain partner in conventional antibodies, HCAb reagents have the
advantage of size and molecular manipulability and are promising tools for drug development and
immunotherapy.
Genes encoding HCAbs evolved separately in two subclasses of cartilaginous fish that diverged 420
million years ago. The role of their HCAbs and pathogen recognition capabilities have not been
characterized, although it has been determined that HCAb convex antigen-combining sites can detect
epitopes inaccessible or bypassed by conventional antibodies. We have discovered novel antibody genes in
a cartilaginous fish whose component gene segments have evolved to encode and rearrange to express
lysines and arginines at the ligand-binding sites. An antibody repertoire whose major antigen-combining
loop is flexible and electropositive is unique among vertebrates, presenting an opportunity to seek antigenic
determinants different from what has been classically defined.
Transgenic mice will be generated to express a set of chimeric fish genes. The first aim of this
proposal is to generate the mutant mice, the second is to test the ability of the transgene repertoire to
respond to various immunogens. Experiments are proposed to test for HCAb detection of novel epitopes in
bacterial capsule and cell wall. Future studies will ascertain their protectiveness against disease.
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Expressing a novel class of heavy chain antibodies
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批准号:10432883
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项目类别:
-
资助金额:$20.19万
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财政年份:2022
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负责人:ELLEN HSU
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依托单位:
Immunoglobulin Constant Region Switch and Hypermutation in the Nurse Shark
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批准号:8008955
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项目类别:
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资助金额:$11.02万
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财政年份:2010
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负责人:ELLEN HSU
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依托单位:
Isotype Exclusion and Hypermutation in the Nurse Shark
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批准号:6728164
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项目类别:
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资助金额:$29.07万
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财政年份:2004
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负责人:ELLEN HSU
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依托单位:
Isotype Exclusion and Hypermutation in the Nurse Shark
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批准号:6838254
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项目类别:
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资助金额:$25.44万
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财政年份:2004
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负责人:ELLEN HSU
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依托单位:
Immunoglobulin Constant Region Switch and Hypermutation in the Nurse Shark
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批准号:8102776
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项目类别:
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资助金额:$34.39万
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财政年份:2004
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负责人:ELLEN HSU
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依托单位:
Isotype Exclusion and Hypermutation in the Nurse Shark
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批准号:7163418
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项目类别:
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资助金额:$24.12万
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财政年份:2004
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负责人:ELLEN HSU
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依托单位:
Immunoglobulin Constant Region Switch and Hypermutation in the Nurse Shark
-
批准号:7736714
-
项目类别:
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资助金额:$34.76万
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财政年份:2004
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负责人:ELLEN HSU
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依托单位:
Immunoglobulin gene expression and recombinational events in the nurse shark
-
批准号:9322603
-
项目类别:
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资助金额:$28.26万
-
财政年份:2004
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负责人:ELLEN HSU
-
依托单位:
Immunoglobulin Constant Region Switch and Hypermutation in the Nurse Shark
-
批准号:8299117
-
项目类别:
-
资助金额:$34.39万
-
财政年份:2004
-
负责人:ELLEN HSU
-
依托单位:
Immunoglobulin gene expression and recombinational events in the nurse shark
-
批准号:9172265
-
项目类别:
-
资助金额:$28.26万
-
财政年份:2004
-
负责人:ELLEN HSU
-
依托单位:
Isotype Exclusion and Hypermutation in the Nurse Shark
-
批准号:7004550
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项目类别:
-
资助金额:$24.84万
-
财政年份:2004
-
负责人:ELLEN HSU
-
依托单位:
海外基金