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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coexpression of two functionally independent p58 inhibitory receptors in human natural killer cell clones results in the inability to kill all normal allogeneic target cells.
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Coexpression of two functionally independent p58 inhibitory receptors in human natural killer cell clones results in the inability to kill all normal allogeneic target cells.

机译：人天然杀伤细胞克隆中两个功能独立的p58抑制受体的共表达导致无法杀死所有正常的同种异体靶细胞。

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摘要

In the present study, we define a group of natural killer (NK) clones (group 0) that fails to lyse all of the normal allogeneic target cells analyzed. Their specificity for HLA class I molecules was suggested by their ability to lyse class I-negative target cells and by the fact that they could lyse resistant target cells in the presence of selected anti-class I monoclonal antibodies. The use of appropriate target cells represented by either HLA-homozygous cell lines or cell transfectants revealed that these clones recognized all the HLA-C alleles. By the use of monoclonal antibodies directed to either GL183 or EB6 molecules, we showed that the EB6 molecules were responsible for the recognition of Cw4 and related alleles, while the GL183 molecules recognized Cw3 (and related C alleles). These data suggest that the GL183 and the EB6 molecules can function, in individual NK clones, as independent receptors for two different groups of HLA-C alleles, (which include all known alleles for locus C), thus resulting in their inability to lyse all normal HLA-C+ target cells. Indirect immunofluorescence and fluorescence-activated cell sorting analysis revealed that the presently defined GL183+EB6+ group 0 NK clones brightly express EB6 molecules (EB6bright) while the GL183+EB6+ group 2 clones (unable to recognize Cw4) express an EB6dull phenotype. These data also imply that the density of EB6 receptors may be critical for the generation of an optimal negative signal upon interaction with appropriate HLA-C alleles.
机译：在本研究中，我们定义了一组自然杀伤（NK）克隆（第0组），这些克隆无法裂解所有分析的正常同种异体靶细胞。通过它们裂解I类阴性靶细胞的能力以及在选定的抗I类单克隆抗体的存在下它们可以裂解抗性靶细胞这一事实表明了它们对HLA I类分子的特异性。以HLA-纯合细胞系或细胞转染子为代表的合适靶细胞的使用表明，这些克隆可识别所有HLA-C等位基因。通过使用针对GL183或EB6分子的单克隆抗体，我们显示EB6分子负责Cw4和相关等位基因的识别，而GL183分子识别Cw3（及相关C等位基因）。这些数据表明，GL183和EB6分子可以在单独的NK克隆中作为两组不同的HLA-C等位基因（包括基因座C的所有已知等位基因）的独立受体发挥作用，从而导致它们无法裂解所有正常的HLA-C +靶细胞。间接免疫荧光和荧光激活细胞分选分析表明，目前定义的GL183 + EB6 +组0 NK克隆明亮地表达EB6分子（EB6bright），而GL183 + EB6 +组2克隆（无法识别Cw4）表达EB6dull表型。这些数据还暗示，与适当的HLA-C等位基因相互作用后，EB6受体的密度对于产生最佳阴性信号可能至关重要。

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