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人锌转运蛋白8的HLA-A~＊0201限制性CTL表位的预测及初步验证 被引量：2

Identification of HLA-A＊0201-restricted CTL epitopes of human ZnT8
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摘要 目的预测和初步鉴定1型糖尿病(T1DM)主要自身抗原锌转运蛋白8(ZnT8)的HLA-A*0201限制性细胞毒性T淋巴细胞(cytotoxic T lymphocytes,CTL)表位,为基于ZnT8抗原表位的特异性免疫治疗奠定基础。方法选取BIMAS预测工具预测该抗原HLA-A*0201限制性结合肽,人工合成待测表位肽,利用T2细胞株测定各肽与HLA-A*0201分子的结合力。利用酶联免疫斑点检测(enzyme-linked immunospotassay,ELISPOT)方法检测候选肽刺激T1DM患者外周血单个核细胞分泌IFN-γ和IL-2的能力,利用标准51Cr释放试验检测特异性CTL诱导活性。结果在所筛选的5个候选CTL表位中,ZnT8(107-115)、ZnT8(115-123)及ZnT8(145-153)与HLA-A*0201分子具有较高的结合荧光强度,可在体外有效诱导抗原特异性CTL的产生,刺激T1DM患者PBMC分泌IFN-γ和IL-2,并对抗原肽负载的T2细胞具有明显的杀伤效应。结论 ZnT8(107-115)、ZnT8(115-123)及ZnT8(145-153)可能是HLA-A*0201限制性CTL表位,为基于人ZnT8抗原表位的特异性免疫治疗奠定理论基础。 This study is aimed to identify HLA-A＊0201-restricted CTL epitopes from human ZnT8,which may lay a foundation for specific immunotherapy based on epitope.We predicted HLA-A＊0201 restricted cytotoxic T lymphocyte（CTL） epitope from BIMAS.Then the predicted peptides were synthesized and purified.Furthermore,T2 cell line was used to determine binding activity of the peptide to HLA-A＊0201 molecule.Finally,five candidate peptides were utilized to elicited CTL response which detected by ELISPOT assay and 51Cr release assays.We found that ZnT8（107-115）,ZnT8（115-123）,and ZnT8（145-153） out of the 5 candidate peptides could bind to HLA-A＊0201 molecule with high affinity.And these peptides could induce specific CTLs in vitro,stimulate peripheral blood mononuclear cell（PBMC） to secrete IFN-γ and IL-2,as well as lyse target cells.All these results suggest that ZnT8（107-115）,ZnT8（115-123）,and ZnT8（145-153） might be the HLA-A＊0201 restricted epitopes of ZnT8,and the results provide a foundation for immunotherapy of ZnT8.
作者 李树法 张敏 陈兵
机构地区 贵阳市第一人民医院内分泌科 中华社区卫生服务中心 第三军医大学西南医院内分泌科
出处 《免疫学杂志》 CAS CSCD 北大核心 2012年第10期880-883,共4页 Immunological Journal
基金 贵州省科技厅基金(黔科合SY【2012】3139 黔科合SY【2011】3049) 贵阳市科技局基金(筑科合【2012103】13 2010筑科农字第1-社-03号)
关键词 HLA-A＊0201 CTL 结合肽 表位 限制性 HLA-A＊0201 Cytotoxic T lymphocyte Connecting peptide Epitopes Restriction
分类号 R392.9 [医药卫生—免疫学]
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参考文献12

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二级参考文献9

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共引文献5

同被引文献26

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免疫学杂志
2012年 第10期

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