Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes.
Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes.
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在肿瘤浸润淋巴细胞上表达的孤儿T细胞受体的抗原鉴定。
DOI：
10.1016/j.cell.2017.11.043
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发表时间：
2018-01-25
期刊：
影响因子：
64.5
通讯作者：
Garcia KC
中科院分区：
文献类型：
--
作者：
Gee MH;Han A;Lofgren SM;Beausang JF;Mendoza JL;Birnbaum ME;Bethune MT;Fischer S;Yang X;Gomez-Eerland R;Bingham DB;Sibener LV;Fernandes RA;Velasco A;Baltimore D;Schumacher TN;Khatri P;Quake SR;Davis MM;Garcia KC
免疫系统可以启动针对肿瘤的T细胞反应；然而，肿瘤浸润性淋巴细胞(TIL)的抗原特异性还不是很清楚。我们使用酵母展示的多肽-人白细胞抗原(Phla)文库来筛选人结直肠癌TIL上表达的孤儿T细胞受体(TCR)的抗原。4个TIL来源的TCR对高度多样化的Phla-A*02：01文库中的多肽显示出很强的选择性。其中三个TIL TCR是针对非突变自身抗原的，其中两个存在于单独的患者肿瘤中，并且共享来自U2AF2的非突变自身抗原的特异性。这些结果表明，TCR可访问的MHC结合肽的暴露识别表面包含足够的结构信息，从而能够重建未知特异性的致病TCR的多肽靶标序列。这一发现强调了TCR对其同源抗原的惊人特异性，这使得通过无偏见的筛查能够轻松地识别肿瘤抗原。一种识别T细胞受体配体的新方法揭示了肿瘤浸润性淋巴细胞的特异性
The immune system can mount T cell responses against tumors; however, the antigen specificities of tumor-infiltrating lymphocytes (TILs) are not well understood. We used yeast-display libraries of peptide-human leukocyte antigen (pHLA) to screen for antigens of ‘orphan’ T cell receptors (TCRs) expressed on TILs from human colorectal adenocarcinoma. Four TIL-derived TCRs exhibited strong selection for peptides presented in a highly diverse pHLA-A*02:01 library. Three of the TIL TCRs were specific for non-mutated self-antigens, two of which were present in separate patient tumors, and shared specificity for a non-mutated self-antigen derived from U2AF2. These results show that the exposed recognition surface of MHC-bound peptides accessible to the TCR contains sufficient structural information to enable reconstruction of sequences of peptide targets for pathogenic TCRs of unknown specificity. This finding underscores the surprising specificity of TCRs for their cognate antigens, which enables the facile identification of tumor antigens through unbiased screening. A new approach for identification T cell receptor ligands reveals insights into the specificity of tumor-infiltrating lymphocytes
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影响因子：
14.9
作者：
Chung IF;Chen CY;Su SC;Li CY;Wu KJ;Wang HW;Cheng WC
通讯作者：
Cheng WC
影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
46.9
作者：
Han, Arnold;Glanville, Jacob;Hansmann, Leo;Davis, Mark M.
通讯作者：
Davis, Mark M.
影响因子：
32.4
作者：
Adams JJ;Narayanan S;Liu B;Birnbaum ME;Kruse AC;Bowerman NA;Chen W;Levin AM;Connolly JM;Zhu C;Kranz DM;Garcia KC
通讯作者：
Garcia KC
影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
通讯作者：
Garcia KC