Hepatitis B surface antigen presentation and HLA-DRB1*-: lessons from twins and peptide binding studies
Hepatitis B surface antigen presentation and HLA-DRB1*-: lessons from twins and peptide binding studies
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DOI：
10.1111/j.1365-2249.2005.02765.x
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发表时间：
2005-05-01
影响因子：
4.6
通讯作者：
Hoehler, T
中科院分区：
文献类型：
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作者：
Kruger, A;Adams, P;Hoehler, T
本研究旨在探讨某些HLA-DRB 1 * 等位基因与HBsAg疫苗免疫应答之间的遗传关联的潜在机制。因此，通过肽结合ELISA在体外测量HBsAg肽与HLA-DR分子的结合。此外，在ELISPOT测定中离体分析了HBsAg特异性T细胞反应和免疫应答的细胞因子谱，并用HBsAg特异性T细胞克隆研究了T细胞增殖应答的DR限制。此外，我们比较了HBsAg疫苗接种后的24个单卵和3个双卵双胞胎对HBsAg特异性T细胞反应。我们的结果表明，肽结合试验不能反映体内抗原呈递。与疫苗接种失败相关的DR等位基因如DRB 1 *0301和0701有效地呈递HBsAg肽。在11的24个调查的单卵双胞胎对，我们观察到明显的差异，在识别HBsAg肽。这项研究表明，HLA-DR与HBsAg疫苗接种反应的关联不是由肽结合的差异或Th 1/Th 2模式的转变引起的。我们的研究结果强烈表明，T细胞对肽/MHC复合物的识别差异是T细胞对HBsAg反应的关键事件。
The aim of this study was to investigate the underlying mechanisms of the genetic association between certain HLA-DRB1* alleles and the immune response to HBsAg vaccination. Therefore, HBsAg peptide binding to HLA-DR molecules was measured in vitro by peptide binding ELISAs. Additionally, HBsAg-specific T cell reaction and cytokine profile of immune response were analysed ex vivo in ELISPOT assays and DR-restriction of T-cell proliferative responses was investigated with HBsAg specific T cell clones. In addition, we compared HBsAg specific T cell responses of 24 monozygotic and 3 dizygotic twin pairs after HBsAg vaccination. Our results showed that the peptide binding assays did not reflect antigen presentation in vivo. DR alleles associated with vaccination failure like DRB1*0301 and 0701 efficiently presented HBsAg peptides. In 11 of 24 investigated monozygotic twin pairs we observed pronounced differences in the recognition of HBsAg peptides. This study indicates that HLA-DR associations with HBsAg vaccination response are not caused by differences in peptide binding or by a shift in the Th1/Th2 profile. Our findings strongly argue for differences in the T cell recognition of peptide/MHC complexes as the critical event in T cell responsiveness to HBsAg.