文章：

健康个体中存在高频针对钙网蛋白外显子9突变的循环记忆T细胞

High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals

原文发布日期：2019-01-17

DOI: 10.1038/s41408-018-0166-4

类型: Article

开放获取: 是

英文摘要：

Mutations in exon 9 of the calreticulin gene (CALR) frequently occur in patients with chronic myeloproliferative neoplasms (MPN). Patients exhibit spontaneous cellular immune responses to epitopes derived from the mutant CALR C-terminus, and CALR-mutant-specific T cells recognize autologous CALR-mutant malignant cells. This study investigated whether CALR-mutant-specific T cells occur naturally in CALRwt MPN-patients and in healthy individuals. Specific immune responses against epitopes in the mutant CALR peptide sequence were detected in both CALRwt MPN-patients and in healthy individuals. Healthy donors displayed more frequent and stronger CALR-mutant specific T-cell responses compared to the responses identified in CALR-mutant MPN-patients. Several T-cell responses were identified in healthy donors directly ex vivo. Importantly, by running functional analyses on live-sorted immune cells from healthy donors, we showed that circulating CALR-mutant-specific immune cells are T-memory cells. These findings suggest, that healthy individuals acquire a CALR exon 9 mutation, but the immune system reacts and clears the mutant cells, and during this reaction generates CALR-mutant specific T-memory cells. We believe that these findings provide the evidence for tumor immune surveillance in MPN.

摘要翻译： 

钙网蛋白基因（CALR）第9外显子突变在慢性骨髓增生性肿瘤（MPN）患者中频繁发生。患者对源自突变CALR C末端的表位表现出自发性细胞免疫应答，并且CALR突变特异性T细胞识别自体CALR突变恶性细胞。本研究调查了CALR突变特异性T细胞是否在CALR野生型MPN患者和健康个体中自然发生。在CALR野生型MPN患者和健康个体中均检测到针对突变CALR肽序列中表位的特异性免疫应答。与CALR突变MPN患者中识别的应答相比，健康供体显示出更频繁和更强的CALR突变特异性T细胞应答。在健康供体中直接离体识别出几种T细胞应答。重要的是，通过对健康供体的活分选免疫细胞进行功能分析，我们表明循环中的CALR突变特异性免疫细胞是T记忆细胞。这些发现表明，健康个体会获得CALR第9外显子突变，但免疫系统会反应并清除突变细胞，并在此反应过程中产生CALR突变特异性T记忆细胞。我们相信这些发现为MPN中的肿瘤免疫监视提供了证据。

原文链接：

High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals