MHC class I molecules on adenovirus E1A-expressing tumor cells inhibit NK cell killing but not NK cell-mediated tumor rejection.
MHC class I molecules on adenovirus E1A-expressing tumor cells inhibit NK cell killing but not NK cell-mediated tumor rejection.
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表达腺病毒 E1A 的肿瘤细胞上的 MHC I 类分子抑制 NK 细胞杀伤，但不抑制 NK 细胞介导的肿瘤排斥。
DOI：
10.1093/intimm/13.10.1301
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发表时间：
2001
影响因子：
4.4
通讯作者：
Nakamura,M
中科院分区：
文献类型：
--
作者：
Routes,JM;Ryan,JC;Ryan,S;Nakamura,M
腺病毒E1 A基因产物在肿瘤细胞中的表达增强了NK细胞的体外裂解和NK介导的体内排斥，尽管增加了肿瘤细胞上的I类分子。目前还不清楚为什么MHC I类分子表达的增加似乎没有赋予对NK细胞杀伤的抗性。一种可能性是E1 A使细胞对多种NK细胞杀伤机制（包括穿孔素/颗粒酶、Fas配体、肿瘤坏死因子-α和TRAIL）敏感的独特能力。为了研究这个问题，用H-2Dd（NK抑制性受体Ly 49 A的配体）转染表达E1 A且对NK敏感的MCA-102-E1 A肿瘤细胞（H-2b）。MCA-102-E1 A细胞表达H-2Dd分子可保护它们免受Ly 49 A +NK细胞克隆和从C57 BL/6裸鼠分离的Ly 49 A +NK细胞的裂解。相比之下，NK细胞介导的MCA-102-E1 A肿瘤细胞排斥反应不受H-2Dd分子表达的抑制，也不受从C57 BL/6-裸小鼠分离的NK细胞多克隆群体的杀伤。H-2Dd与C57 BL/6小鼠NK细胞上非克隆表达的几种抑制性Ly 49受体相互作用：Ly 49 A（20%的NK细胞），Ly 49 G2（54%的NK细胞）和Ly 49 C/I（47%的NK细胞）。我们的数据表明，虽然E1 A敏感的NK细胞杀伤细胞，它不干扰抑制性NK受体的信号转导。因此，不表达Ly 49 A、Ly 49 G2或Ly 49 C/I抑制性受体的一小部分NK细胞可能负责MCA-102-E1 A-DD肿瘤细胞在体内的排斥。
Expression of adenovirus E1A gene products in tumor cells enhances NK cell lysisin vitroand NK-mediated rejectionin vivo, despite increasing class I molecules on tumor cells. It is unclear why the increased expression of MHC class I molecules does not appear to confer resistance to killing by NK cells. One possibility is the unique capacity of E1A to sensitize cells to multiple NK cell killing mechanisms including perforin/granzyme, Fas ligand, tumor necrosis factor-α and TRAIL. To examine this issue, MCA-102-E1A tumor cells (H-2b) that express E1A and are NK sensitive were transfected with H-2Dd, the ligand for the NK inhibitory receptor, Ly49A. Expression of H-2Ddmolecules by MCA-102-E1A cells protected them from lysis by a Ly49A+NK cell clone and Ly49A+NK cells isolated from C57BL/6 nude mice. In contrast, NK cell-mediated rejection of MCA-102-E1A tumor cells was not inhibited by the expression of H-2Ddmolecules, nor was killing by polyclonal populations of NK cells isolated from C57BL/6-nude mice. H-2Ddinteracts with several inhibitory Ly49 receptors that are non-clonally expressed on NK cells in C57BL/6 mice: Ly49A (20% of NK cells), Ly49G2 (54% of NK cells) and Ly49C/I (47% of NK cells). Our data indicate that while E1A sensitizes cells to NK cell killing, it does not interfere with signal transduction by inhibitory NK receptors. Therefore, a small population of NK cells that do not express Ly49A, Ly49G2 or Ly49C/I inhibitory receptors are likely responsible for the rejection of MCA-102-E1A-Ddtumor cellsin vivo.