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Enhanced activation of human T cell clones specific for virus-like particles expressing the HIV V3 loop in the presence of HIV V3 loop-specific polyclonal antibodies

机译:在存在HIV V3环特异性多克隆抗体的情况下增强了对表达HIV V3环的病毒样颗粒特异的人类T细胞克隆的激活

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摘要

Recombinant virus-like particles (VLP), formed by the yeast Ty p1 protein, carrying the HIV gp120 V3 loop on their surface (V3-VLP) have been tested in vitro for immunogenicity and antigenicity by using VLP p1-specific human CD4+ T cell lines and clones. VLP-specific human T cell lines and clones were generated from normal individuals, indicating that VLP-specific precursor cells present in the peripheral lymphocyte pool can be induced to expand clonally upon antigen challenge in vitro, in the absence of previous immunization. It was also shown that V3-specific polyclonal antibodies enhance V3-VLP-induced activation of VLP-specific T cell clones. Antibody-dependent potentiation has been shown previously in other antigen systems, and it depends on enhanced uptake of complexed antigen by Fc receptor-positive antigen-presenting cells. Since in this case antigen is internalized by presenting cells as a complex, it can be inferred that a similar event of antibody-mediated antigen uptake can take place with V3-specific B cells, resulting in presentation by the B cells of T helper epitopes derived from processing of the VLP p1 moiety. This suggests that T helper cells specific for the carrier VLP p1 protein can be activated to provide help to V3-specific B cells in the presence of the appropriate antigen construct.
机译:酵母Ty p1蛋白形成的重组病毒样颗粒(VLP)的表面带有HIV gp120 V3环(V3-VLP)已通过使用VLP p1特异性人类CD4 + T细胞系和克隆。 VLP特异的人T细胞系和克隆是从正常个体产生的,这表明在没有事先免疫的情况下,在体外抗原攻击后,可以诱导外周淋巴细胞池中存在的VLP特异的前体细胞克隆扩增。还显示出V3特异性多克隆抗体增强了V3-VLP诱导的VLP特异性T细胞克隆的活化。先前已在其他抗原系统中显示了抗体依赖性增强作用,它依赖于Fc受体阳性抗原呈递细胞对复合抗原的吸收增强。由于在这种情况下,抗原通过呈递复合物呈递细胞而被内在化,因此可以推断,V3特异性B细胞可能发生类似的抗体介导的抗原摄取事件,导致B细胞呈递T辅助抗原决定簇来自VLP p1部分的加工。这表明在合适的抗原构建体存在的情况下,可以激活特异于载体VLP p1蛋白的T辅助细胞,从而为V3特异性B细胞提供帮助。

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