Orientation of epitopes influences the immunogenicity of synthetic peptide dimmers
Orientation of epitopes influences the immunogenicity of synthetic peptide dimmers
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表位的方向影响合成肽二聚体的免疫原性
DOI：
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发表时间：
1988
影响因子：
5.4
通讯作者：
M. Francis
中科院分区：
文献类型：
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作者：
J. Cox;J. Ivanyi;D. Young;J. Lamb;A. Syred;M. Francis
在近交系小鼠中检查了基于源自分枝杆菌65-kDa抗原和口蹄疫病毒（FMDV）VP 1蛋白的表位序列的合成肽二聚体的免疫原性。该分析针对T细胞刺激性分枝杆菌表位（65-85）相对于来自相同分子（422-436）或来自VP 1（141-160）的免疫原性差的位点的潜在辅助作用。65-85重复同二聚体在CBA/ca中诱导抗体应答，但在C57 BL/6小鼠中不诱导，这两种小鼠均对65-85单体无应答，并在BALB/c单体应答小鼠中扩增抗体应答。杂交二聚体在BALB/c小鼠中的免疫原性的分析表明，二聚体内的肽的取向对于所产生的抗体应答的程度是至关重要的。只有422-436/65-85而不是65-85/422-436诱导抗体与422-436序列结合，当作为单体或二聚体注射时，422-436序列是非免疫原性的。尽管免疫原性存在显著差异，但两种检测的杂交二聚体在固相免疫测定中与65-85-二聚体或422-436/65-85肽的抗血清或与422-436表位的单克隆抗体反应相同。所描述的抗体反应性的差异也不能仅仅归因于T细胞刺激的程度，因为对于所有相关的肽组合，增殖反应都是均匀表达的。65-85二聚体和422-436165-85杂交体的抗血清也与天然65-kDa蛋白反应。此外，在141 - 160无应答B10.D2小鼠中响应141 -160（VP 1衍生的）/ 65-85杂合肽的FMDV中和抗体的产生也证实了65-85表位的辅助活性。因此，将异源肽与分枝杆菌65-85序列的N末端组合通常可适用于肽疫苗的增强。
The immunogenicity of synthetic peptide dimers based on epitope sequences derived from the mycobacterial 65‐kDa antigen and the foot and mouth disease virus (FMDV) VP1 protein was examined in inbred mice. The analysis was directed towards the potential helper role of a T cell stimulatory mycobacterial epitope (65–85) with respect to poorly immunogenic sites either from the same molecule (422–436) or from VP1 (141–160). The 65–85 repeat homodimer induced an antibody response in CBA/ca but not in C57BL/6 mice, both nonresponders to the 65–85 monomer, and amplified the antibody response in BALB/c, monomer‐responder mice. Analysis of the immunogenicity of hybrid dimers in BALB/c mice showed that the orientation of peptides within the dimer is critical for the extent of the produced antibody response. Only the 422–436/65–85 but not the 65–85/422–436 induced antibodies binding to the 422–436 sequence which was nonimmunogenic when injected either as a monomer or dimer. Despite the striking difference in immunogenicity, both tested hybrid dimers reacted equally in the solid‐phase immunoassay with antisera raised to 65–85‐dimer or 422–436/65–85 peptides or with a monoclonal antibody to the 422–436 epitope. The described differences in antibody responsiveness also cannot be attributed merely to the extent of T cell stimulation since the proliferative responses were uniformly expressed for all relevant combinations of peptides. Antisera to 65–85 dimer and 422–436165–85 hybrid also reacted with the native 65‐kDa protein. Furthermore, the production of FMDV‐neutralizing antibodies in response to the 141–160 (VP1‐derived)/ 65–85 hybrid peptide in 141–160 nonresponder B10.D2 mice also confirmed the helper activity of the 65–85 epitope. Thus, combining heterologous peptides with the N‐terminal of the mycobacterial 65–85 sequence may be generally applicable for the potentiation of peptide vaccines.
DOI：
10.1073/pnas.83.18.7013
发表时间：
1986-09-01
影响因子：
11.1
作者：
MEHRA, V;SWEETSER, D;YOUNG, RA
通讯作者：
YOUNG, RA
DOI：
10.1073/pnas.82.15.5131
发表时间：
1985-01-01
影响因子：
11.1
作者：
HOUGHTEN, RA
通讯作者：
HOUGHTEN, RA
T 细胞对单纯疱疹病毒糖蛋白 D 的反应：抗原构象的意义。
DOI：
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发表时间：
1985
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Heber-Katz,E;Hollosi,M;Dietzschold,B;Hudecz,F;Fasman,GD
通讯作者：
Fasman,GD