Distinct structural TCR repertoires in naturally occurring versus vaccine-induced CD8+ T-Cell responses to the tumor-specific antigen NY-ESO-1
Distinct structural TCR repertoires in naturally occurring versus vaccine-induced CD8+ T-Cell responses to the tumor-specific antigen NY-ESO-1
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DOI：
10.1097/01.cji.0000161398.34701.26
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发表时间：
2005-05-01
影响因子：
3.9
通讯作者：
Valmori, D
中科院分区：
文献类型：
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作者：
Le Gal, FA;Ayyoub, M;Valmori, D
对癌症睾丸抗原NY-ESO-1的自发免疫应答经常在携带抗原表达肿瘤的癌症患者中发现。在表达HLA-A2的患者中，天然引发的NY-ESO-1特异性肿瘤反应性细胞毒性T淋巴细胞（CTL）主要针对对应于肽NY-ESO-1157 -165的免疫显性表位。NY-ESO-1特异性CTL也可由合成肽疫苗诱导。但它们在功能亲合力和肿瘤反应性方面是异质的，作者通过分析天然和疫苗诱导的NY-ESO-1特异性CTL的TCR特征来研究这种现象的结构基础。结果表明，来自两组的CTL表现出高度结构保守但不同的TCR特征，表明用于疫苗接种的合成肽可以忠实地模拟天然加工的抗原。总之，本研究的结果强调了TCR分子监测的强度，并将有助于开发和监测旨在引发具有高肿瘤反应性的CTL的疫苗。
Spontaneous immune responses to the cancer testis antigen NY-ESO-1 are frequently found in cancer patients bearing antigen-expressing tumors. In HLA-A2-expressing patients, naturally elicited NY-ESO-1-specific, tumor-reactive cytotoxic T lymphocytes (CTLs) are mostly directed against an immunodominant epilope corresponding to peptide NY-ESO-1 157-165. NY-ESO-1-specific CTLs can also be induced by synthetic peptide vaccines. but they are heterogeneous in terms of functional avidity and tumor reactivity, The authors investigated the structural bases of this phenomenon by analyzing the TCR features of natural and vaccine-induced NY-ESO-1-specific CTLs. The results indicate that CTLs from the two groups exhibit highly structurally conserved but distinct TCR features, suggesting that the synthetic peptides used for vaccination may rail to faithfully mimic the naturally processed antigen. Together, the results of this study underline the strength of TCR molecular monitoring and will be instrumental for the development and monitoring of vaccines aimed at eliciting CTLs with high tumor reactivity.