HLA-C IS THE INHIBITORY LIGAND THAT DETERMINES DOMINANT RESISTANCE TO LYSIS BY NK1-SPECIFIC AND NK2-SPECIFIC NATURAL-KILLER-CELLS
HLA-C IS THE INHIBITORY LIGAND THAT DETERMINES DOMINANT RESISTANCE TO LYSIS BY NK1-SPECIFIC AND NK2-SPECIFIC NATURAL-KILLER-CELLS
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DOI：
10.1073/pnas.90.24.12000
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发表时间：
1993-12-15
影响因子：
11.1
通讯作者：
STROMINGER, JL
中科院分区：
文献类型：
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作者：
COLONNA, M;BORSELLINO, G;STROMINGER, JL
自然杀伤 (NK) 细胞识别正常细胞上的同种异体抗原。这些同种异体抗原之一与 HLA-C 在位置 77-80 的二态性纯合性相关，这是许多 HLA-C 等位基因共有的。第二个等位基因同种抗原与替代 HLA-C 二态性的纯合性相关，其余 HLA-C 等位基因共有该二态性。此外，NK1和NK2特异性NK细胞系可以通过混合白细胞培养物产生，其中供体和刺激物对于HLA-C位置77-80处的替代二态性是纯合的。在目前的工作中，通过分析几个 HLA-C 等位基因转染对 I 类缺失突变细胞系 NK 敏感性产生的影响，直接研究了 HLA-C 在 NK 细胞介导的同种异体识别中的作用。用编码 Asn-77-Lys-80（包括 HLA-Cw4、-Cw5 和 -Cw6）的 HLA-C 等位基因转染细胞可抑制 NK1 特异性 NK 细胞对靶标的裂解，而编码 Ser-77-Asn-80（包括 HLA-Cw1、-Cw7 和 -Cw13）的 HLA-C 等位基因可保护靶标免受 NK2 特异性 NK 细胞的侵害。因此，HLA-C 等位基因是主要的抑制性配体，可保护靶标免受这些同种异体特异性 NK 细胞的裂解。
Natural killer (NK) cells recognize alloantigens on normal cells. One of these alloantigens correlates with homozygosity for a dimorphism of HLA-C at positions 77-80, which is shared by a number of HLA-C alleles. A second allelic alloantigen correlates with homozygosity for the alternative HLA-C dimorphism, which is shared by the remaining HLA-C alleles. Moreover, NK1- and NK2-specific NK cell lines can be generated by mixed leukocyte cultures in which donor and stimulator are homozygous for the alternative dimorphisms at positions 77-80 of HLA-C. In the present work, the role of HLA-C in NK cell-mediated allorecognition was directly investigated by analyzing the effects produced by transfection of several HLA-C alleles on NK sensitivity of class I-deleted mutant cell lines. Transfection of cells with HLA-C alleles encoding Asn-77-Lys-80 (including HLA-Cw4, -Cw5, and -Cw6) inhibited the lysis of the targets by NK1-specific NK cells, whereas HLA-C alleles encoding Ser-77-Asn-80 (including HLA-Cw1, -Cw7, and -Cw13) protected the targets from NK2-specific NK cells. Thus, HLA-C alleles are the dominant inhibitory ligands that protect targets from lysis by these allospecific NK cells.