Self-peptides with intermediate capacity to bind and stabilize MHC class I molecules may be immunogenic
Self-peptides with intermediate capacity to bind and stabilize MHC class I molecules may be immunogenic
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DOI：
10.1046/j.1365-3083.2003.01182.x
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发表时间：
2003-01-01
影响因子：
3.7
通讯作者：
Claesson, MH
中科院分区：
文献类型：
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作者：
Andersen, MLM;Ruhwald, M;Claesson, MH
根据它们与H-2（B）分子的预测结合选择了30种自身肽。通过生物化学（K（D）测量）和细胞[主要组织相容性复合体I类（MHC-I）稳定性]测定，在实验上确定肽的结合。观察到K（D）测量值与MHC-I稳定性之间的弱但显著的相关性。用单独的肽免疫小鼠（n = 99）。发现28个肽诱导肽特异性细胞毒活性，并且总共84只小鼠在免疫后产生显著的细胞毒性T淋巴细胞（CTL）应答。用高亲和力肽免疫的21只小鼠中只有一只产生了每10（6）个脾细胞29个裂解单位的肽特异性CTL应答，而用中等亲和力肽免疫的42只小鼠中有11只产生了该水平的肽特异性CTL应答（P < 0.05）。这些观察结果表明对大多数MHC-I限制性自身肽不存在耐受性，并且可以优先产生对MHC-I具有中等亲和力的自身肽的强抗自身免疫。这些数据应在基于MHC-I结合自身肽的肿瘤疫苗的设计中加以考虑。
Thirty self-peptides were selected on the basis of their predicted binding to H-2(b) molecules. The binding of peptides was ascertained experimentally by biochemical (K (D) measurements) and cellular [major histocompatibility complex class I (MHC-I) stabilization] assays. A weak, but significant, correlation between K (D) measurements and MHC-I stabilization was observed. Mice (n = 99) were immunized with individual peptides. Twenty-eight peptides were found to induce peptide-specific cytotoxic activity, and a total of 84 mice developed significant cytotoxic T lymphocyte (CTL) responses after immunization. Only one of the 21 mice immunized with high-affinity peptides developed a peptide-specific CTL response of 29 lytic units per 10(6) splenocytes, whereas 11 of the 42 mice immunized with intermediate-affinity peptides developed peptide-specific CTL responses at this level (P < 0.05). These observations suggest the absence of tolerance towards most MHC-I-restricted self-peptides and that strong antiself immunity can be generated preferentially towards self-peptides with an intermediate affinity for MHC-I. These data should be considered in the design of tumour vaccines based on MHC-I-binding self-peptides.