Differential antigenic requirements by diverse MR1-restricted T cells.
Differential antigenic requirements by diverse MR1-restricted T cells.
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DOI：
10.1111/imcb.12519
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发表时间：
2022-03
影响因子：
4
通讯作者：
Gherardin, Nicholas A.
中科院分区：
文献类型：
--
作者：
Seneviratna, Rebecca;Redmond, Samuel J.;McWilliam, Hamish E. G.;Reantragoon, Rangsima;Villadangos, Jose A.;McCluskey, James;Godfrey, Dale, I;Gherardin, Nicholas A.
MHC相关蛋白1(MR1)将微生物核黄素代谢产物提供给粘膜相关不变T细胞(MAIT)，以监测微生物的存在。MAIT细胞表达一种半不变的T细胞受体(TCR)，它以类似模式识别的方式识别MR1抗原复合体。最近，不同群体的MR1限制性T细胞表现出对肿瘤细胞的广泛识别，并似乎识别与肿瘤自身抗原相关的MR1，尽管这些抗原的身份尚不清楚。在这里，我们使用TCR基因转移和工程表达MR1的抗原提呈细胞来探测一系列MR1限制性TCR的MR1限制性和抗原反应性，包括模型肿瘤反应性TCRs。我们通过这些TCR证实了MR1的活性，显示出对MR1(K43)第43位赖氨酸的不同依赖，并显示出MR1配体6-甲酰蝶呤的竞争抑制作用。然而，表达TCR的报告系未能概括先前报道的强大的肿瘤特异性，这表明辅助分子对MR1依赖的肿瘤反应性具有重要作用。最后，mr1突变细胞系表明，不同mr1限制性T细胞与α1/α2螺旋上不同的残基需要不同的残基，这表明mr1限制性αβtcr的广泛家族存在中心但不同的对接模式。总的来说，这些数据与不同的MR1限制性T细胞对不同抗原的识别是一致的。该研究为肿瘤反应性MHC相关蛋白1(MR1)限制性T细胞的自身反应性提供了证据。此外，我们发现这些T细胞受体表现出不同的抗原识别能力，并利用不同的对接模式识别MR1抗原复合体。
MHC‐related protein 1 (MR1) presents microbial riboflavin metabolites to mucosal‐associated invariant T (MAIT) cells for surveillance of microbial presence. MAIT cells express a semi‐invariant T‐cell receptor (TCR), which recognizes MR1–antigen complexes in a pattern‐recognition‐like manner. Recently, diverse populations of MR1‐restricted T cells have been described that exhibit broad recognition of tumor cells and appear to recognize MR1 in association with tumor‐derived self‐antigens, though the identity of these antigens remains unclear. Here, we have used TCR gene transfer and engineered MR1‐expressing antigen‐presenting cells to probe the MR1 restriction and antigen reactivity of a range of MR1‐restricted TCRs, including model tumor‐reactive TCRs. We confirm MR1 reactivity by these TCRs, show differential dependence on lysine at position 43 of MR1 (K43) and demonstrate competitive inhibition by the MR1 ligand 6‐formylpterin. TCR‐expressing reporter lines, however, failed to recapitulate the robust tumor specificity previously reported, suggesting an importance of accessory molecules for MR1‐dependent tumor reactivity. Finally, MR1‐mutant cell lines showed that distinct residues on the α1/α2 helices were required for TCR binding by different MR1‐restricted T cells and suggested central but distinct docking modes by the broad family of MR1‐restricted αβ TCRs. Collectively, these data are consistent with recognition of distinct antigens by diverse MR1‐restricted T cells. The study provides evidence validating the self‐reactivity of tumor‐reactive MHC‐related protein 1 (MR1)‐restricted T cells. Furthermore, we show that these T‐cell receptors exhibit differential antigen recognition and utilize diverse docking modes to recognize MR1–antigen complexes.
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影响因子：
56.9
作者：
HASHIMOTO, K;HIRAI, M;KUROSAWA, Y
通讯作者：
KUROSAWA, Y
影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
24.8
作者：
Harriff MJ;McMurtrey C;Froyd CA;Jin H;Cansler M;Null M;Worley A;Meermeier EW;Swarbrick G;Nilsen A;Lewinsohn DA;Hildebrand W;Adams EJ;Lewinsohn DM
通讯作者：
Lewinsohn DM
DOI：
10.1093/protein/gzg087
发表时间：
2003-09-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Boulter, JM;Glick, M;Jakobsen, BK
通讯作者：
Jakobsen, BK