CD66a interactions between human melanoma and NK cells: A novel class I MHC-independent inhibitory mechanism of cytotoxicity
CD66a interactions between human melanoma and NK cells: A novel class I MHC-independent inhibitory mechanism of cytotoxicity
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DOI：
10.4049/jimmunol.168.6.2803
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发表时间：
2002-03-15
影响因子：
4.4
通讯作者：
Mandelboim, O
中科院分区：
文献类型：
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作者：
Markel, G;Lieberman, N;Mandelboim, O
NK细胞能够通过一组裂解受体杀死病毒感染的细胞和肿瘤细胞。表达I类MHC蛋白的细胞被保护免于裂解，主要是由于NK受体的几个家族与经典和非经典I类MHC蛋白的相互作用。在这项研究中，我们表明，I类MHC缺陷型黑色素瘤细胞系（1106mel）染色与几个Ig融合的裂解受体，表明适当的裂解配体的表达。然而，令人惊讶的是，这种黑素瘤细胞系没有被CD16阴性NK克隆杀死。杀伤的缺乏被证明是黑色素瘤细胞系和NK细胞之间的同型CD66a相互作用的结果。此外，表达CD66a蛋白的721.221细胞被YTS细胞和表达CD66a蛋白的NK细胞保护免于裂解。重定向裂解实验表明，抑制作用的强度与CD66a表达水平相关。最后，在来自恶性黑色素瘤患者的NK细胞上观察CD66a蛋白的表达。这些发现表明，存在一种新的I类MHC独立的抑制机制的人NK细胞的细胞毒性。这可能是一些I类MHC阴性黑色素瘤细胞用来逃避CD66a阳性NK细胞攻击的机制。
NK cells are able to kill virus-infected and tumor cells via a panel of lysis receptors. Cells expressing class I MHC proteins are protected from lysis primarily due to the interactions of several families of NK receptors with both classical and nonclassical class I MHC proteins. In this study we show that a class I MHC-deficient melanoma cell line (1106mel) is stained with several Ig-fused lysis receptors, suggesting the expression of the appropriate lysis ligands. Surprisingly, however, this melanoma line was not killed by CD16-negative NK clones. The lack of killing is shown to be the result of homotypic CD66a interactions between the melanoma line and the NK cells. Furthermore, 721.221 cells expressing the CD66a protein were protected from lysis by YTS cells and by NK cells expressing the CD66a protein. Redirected lysis experiments demonstrated that the strength of the inhibitory effect is correlated with the levels of CD66a expression. Finally, the expression of CD66a protein was observed on NK cells derived from patients with malignant melanoma. These findings suggest the existence of a novel class I MHC-independent inhibitory mechanism of human NK cell cytotoxicity. This may be a mechanism that is used by some of the class I MHC-negative melanoma cells to evade attack by CD66a-positive NK cells.