Petersen J W, Holm A, Ibsen P H, Hasløv K, Heron I
Bacterial Vaccine Department, Statens Seruminstitut, Copenhagen, Denmark.
Infect Immun. 1993 Jan;61(1):56-63. doi: 10.1128/iai.61.1.56-63.1993.
The aim of the present study was to identify murine T-cell epitopes on pertussis toxin subunit S4. Six mouse strains with five different haplotypes at the H-2 locus were immunized with the pertussis toxin B oligomer. Lymph node lymphocytes were isolated and stimulated in an in vitro proliferation assay with pertussis toxin components and 11 overlapping synthetic peptides synthesized on the basis of the primary sequence of S4. In vitro proliferative responses to the synthetic peptides revealed the presence of four distinct murine T-cell epitopes on subunit S4. The recognition of the peptides was major histocompatibility complex restricted. Immunizing four of the six mouse strains with the synthetic peptides showed that the peptides which were demonstrated to contain T-cell epitopes following immunization with the B oligomer were able to induce proliferative responses to detoxified pertussis toxin and pertussis toxin components containing subunit S4. One of the identified murine T-cell epitopes corresponded to one of the major human T-cell epitopes previously identified on subunit S4. It is hoped that this murine model system will facilitate the development of a synthetic immunogen mimicking the protective properties of pertussis toxin.
本研究的目的是鉴定百日咳毒素S4亚基上的小鼠T细胞表位。用百日咳毒素B寡聚体免疫6个在H-2位点具有5种不同单倍型的小鼠品系。分离淋巴结淋巴细胞,并在体外增殖试验中用百日咳毒素成分和根据S4的一级序列合成的11种重叠合成肽进行刺激。对合成肽的体外增殖反应显示S4亚基上存在4个不同的小鼠T细胞表位。对这些肽的识别受主要组织相容性复合体限制。用合成肽免疫6个小鼠品系中的4个,结果表明在用B寡聚体免疫后证明含有T细胞表位的肽能够诱导对脱毒百日咳毒素和含有S4亚基的百日咳毒素成分的增殖反应。其中一个鉴定出的小鼠T细胞表位与先前在S4亚基上鉴定出的主要人类T细胞表位之一相对应。希望这个小鼠模型系统将有助于开发一种模拟百日咳毒素保护特性的合成免疫原。