Höhler T, Meyer C U, Notghi A, Stradmann-Bellinghausen B, Schneider P M, Starke R, Zepp F, Sänger R, Clemens R, Meyer zum Büschenfelde K H, Rittner C
I. Department of Internal Medicine, Johannes Gutenberg University Mainz, Germany.
Hum Immunol. 1998 Apr;59(4):212-8. doi: 10.1016/s0198-8859(98)00014-7.
Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell compartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Results obtained in this first study were tested in a second study with 56 responders and 62 nonresponders from an infant vaccination trial. In addition, the peripheral Vbeta-chain T-cell receptor repertoire was investigated using monoclonal antibodies and flow-cytometry in 26 adult responders and 38 nonresponders. As previously reported, nonresponsiveness to HBsAg vaccination was associated with DRB13 and DRB17. In addition, DRB113 was significantly increased among vaccine responders (35.2% vs 5.4%;p < 0.0001) suggesting an immune response promoting effect for this allele whereas the closely related allele DRB114 was associated with nonresponse in the infant study. There was no evidence for a hole in the T cell receptor Vbeta repertoire. In conclusion, in agreement with results obtained in mice there appears to be a hierarchy of DRB1* genes in the HBsAg immune response. The possible differential association of DRB113 and DRB114 may allow the identification of differences between responsiveness and nonresponsiveness to a few amino acid differences in the beta1-domain of the class II heterodimer.
5%-10%的乙肝表面抗原(HBsAg)疫苗接种者对疫苗无反应,这可能是由辅助性T细胞区室缺陷引起的。对HBsAg的免疫反应受主要组织相容性复合体基因的影响。我们研究了53名成年有反应者和73名无反应者的MHC I类和II类抗原。在第一项研究中获得的结果在第二项研究中进行了验证,第二项研究的对象是来自婴儿疫苗接种试验的56名有反应者和62名无反应者。此外,使用单克隆抗体和流式细胞术研究了26名成年有反应者和38名无反应者外周血Vβ链T细胞受体库。如先前报道,对HBsAg疫苗接种无反应与DRB13和DRB17有关。此外,DRB113在疫苗有反应者中显著增加(35.2%对5.4%;p<0.0001),表明该等位基因具有促进免疫反应的作用,而在婴儿研究中,密切相关的等位基因DRB114与无反应有关。没有证据表明T细胞受体Vβ库存在空缺。总之,与在小鼠中获得的结果一致,在HBsAg免疫反应中似乎存在DRB1基因等级。DRB113和DRB1*14可能存在的差异关联可能有助于识别对II类异二聚体β1结构域中几个氨基酸差异的反应性和无反应性之间的差异。