2B4 acts as a non-major histocompatibility complex binding inhibitory receptor on mouse natural killer cells.
2B4 acts as a non-major histocompatibility complex binding inhibitory receptor on mouse natural killer cells.
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2B4 作为小鼠自然杀伤细胞上的非主要组织相容性复合物结合抑制受体。
DOI：
10.1084/jem.20031989
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发表时间：
2004-05-03
期刊：
影响因子：
--
通讯作者：
Kumar V
中科院分区：
文献类型：
--
作者：
Lee KM;McNerney ME;Stepp SE;Mathew PA;Schatzle JD;Bennett M;Kumar V
自然杀伤（NK）细胞在对肿瘤细胞、病毒感染细胞以及骨髓同种异体移植物的免疫应答中至关重要。2B4（CD244）在所有NK细胞上表达，2B4的配体CD48在造血细胞上表达。用抗2B4单克隆抗体使NK细胞上的2B4交联，可在体外导致NK细胞活化。因此，2B4被认为是一种活化受体。令人惊讶的是，我们通过使用抗体阻断以及2B4缺陷型NK细胞发现，2B4的连接会抑制NK细胞对CD48⁺肿瘤细胞和同种异体靶细胞的裂解。NK细胞产生干扰素γ也受到抑制。利用腹腔肿瘤清除实验，发现2B4⁻/⁻小鼠体内对CD48⁺肿瘤细胞的清除增加。2B4的逆转录病毒转导足以在2B4⁻/⁻原代NK细胞中恢复抑制作用。研究发现，尽管成熟的NK细胞表达SH2D1A，但体外培养产生的NK细胞不表达。然而，这两种细胞群都受到2B4连接的抑制。这表明无论是否存在SH2D1A，2B4的抑制性信号传导都会发生。这些发现揭示了2B4作为一种非主要组织相容性复合体结合的NK细胞负调节因子的新作用。
Natural killer (NK) cells are critical in the immune response to tumor cells, virally infected cells, and bone marrow allografts. 2B4 (CD244) is expressed on all NK cells and the ligand for 2B4, CD48, is expressed on hematopoietic cells. Cross-linking 2B4 on NK cells with anti-2B4 monoclonal antibody leads to NK cell activation in vitro. Therefore, 2B4 is considered to be an activating receptor. Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48+ tumor and allogeneic targets is inhibited by 2B4 ligation. Interferon γ production by NK cells is also inhibited. Using a peritoneal tumor clearance assay, it was found that 2B4−/− mice have increased clearance of CD48+ tumor cells in vivo. Retroviral transduction of 2B4 was sufficient to restore inhibition in 2B4−/− primary NK cells. It was found that although mature NK cells express SH2D1A, in vitro–derived NK cells do not. However, both populations are inhibited by 2B4 ligation. This indicates that 2B4 inhibitory signaling occurs regardless of the presence of SH2D1A. These findings reveal a novel role for 2B4 as a non–major histocompatibility complex binding negative regulator of NK cells.
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影响因子：
4.4
作者：
Benoit, L;Wang, XX;Tan, R
通讯作者：
Tan, R
影响因子：
4.4
作者：
Chuang, SS;Kumaresan, PR;Mathew, PA
通讯作者：
Mathew, PA
影响因子：
30.8
作者：
Coffey, AJ;Brooksbank, RA;Bentley, DR
通讯作者：
Bentley, DR
DOI：
10.1084/jem.181.4.1445
发表时间：
1995-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Haynes BF;Heinly CS
通讯作者：
Heinly CS
影响因子：
4.4
作者：
Lee, KM;Bhawan, S;Kumar, V
通讯作者：
Kumar, V