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两种具有高免疫原性和抗原性的肌红蛋白肽及其环化作用

Two large immunogenic and antigenic myoglobin peptides and the effects of cyclisation.

作者信息

Dorow D S, Shi P T, Carbone F R, Minasian E, Todd P E, Leach S J

出版信息

Mol Immunol. 1985 Nov;22(11):1255-64. doi: 10.1016/0161-5890(85)90044-6.

DOI:10.1016/0161-5890(85)90044-6
PMID:4079944
Abstract

Peptides corresponding to sequences (72-88) and (26-54) of beef myoglobin have been synthesised in their open-chain and cyclised forms (using a disulphide bridge) and tested for their antigenicity and immunogenicity. Antibodies raised to beef myoglobin bound to both peptides but more strongly to the 29-residue than to the 17-residue peptide. Cyclisation increased the antigenicity of the larger peptide. In this form the peptide competed much more strongly than in the uncyclised form for specific antibodies to beef myoglobin. The peptides are immunogenic in mice without being coupled to a protein carrier and produce antibodies which bind to beef myoglobin. Peptide (26-54) is the more immunogenic in producing a larger antibody titre to the parent myoglobin and cyclisation again enhances this property. The findings lend weight to the view that longer peptide sequences might be expected to favour the folded state, therefore binding more strongly to antibodies raised to the native protein and eliciting a population of antibodies which contain a larger proportion specific for that conformation. Cyclisation enhances antigenicity and immunogenicity presumably by decreasing the number of degrees of conformational freedom of a peptide without excluding native-like conformations.

摘要

已合成对应于牛肉肌红蛋白序列(72 - 88)和(26 - 54)的肽,分别制成开链形式和环化形式(利用二硫键),并对其抗原性和免疫原性进行了测试。针对牛肉肌红蛋白产生的抗体与这两种肽均有结合,但与29个残基的肽结合更强,而与17个残基的肽结合较弱。环化增加了较大肽的抗原性。以这种形式,该肽比未环化形式更能强烈地竞争针对牛肉肌红蛋白的特异性抗体。这些肽在未与蛋白质载体偶联的情况下对小鼠具有免疫原性,并产生能与牛肉肌红蛋白结合的抗体。肽(26 - 54)在产生针对亲本肌红蛋白的更高抗体滴度方面免疫原性更强,环化再次增强了这一特性。这些发现支持了这样一种观点,即较长的肽序列可能更有利于折叠状态,因此与针对天然蛋白质产生的抗体结合更强,并引发一群对该构象具有更大比例特异性的抗体。环化大概是通过减少肽的构象自由度数量而不排除类似天然的构象来增强抗原性和免疫原性。

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