GENERAL ROLE OF HLA CLASS-I MOLECULES IN THE PROTECTION OF TARGET-CELLS FROM LYSIS BY NATURAL-KILLER-CELLS - EVIDENCE THAT THE FREE HEAVY-CHAINS OF CLASS-I MOLECULES ARE NOT SUFFICIENT TO MEDIATE THE PROTECTIVE EFFECT
GENERAL ROLE OF HLA CLASS-I MOLECULES IN THE PROTECTION OF TARGET-CELLS FROM LYSIS BY NATURAL-KILLER-CELLS - EVIDENCE THAT THE FREE HEAVY-CHAINS OF CLASS-I MOLECULES ARE NOT SUFFICIENT TO MEDIATE THE PROTECTIVE EFFECT
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DOI：
10.1093/intimm/7.3.393
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发表时间：
1995-03-01
影响因子：
4.4
通讯作者：
MORETTA, L
中科院分区：
文献类型：
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作者：
CICCONE, E;PENDE, D;MORETTA, L
一些HLA-C等位基因已经显示出发挥特异性保护作用，防止靶细胞被显示出确定特异性的自然杀伤（NK）克隆群裂解。在这项研究中，我们分析了I类介导的保护是否是涉及所有NK细胞的更普遍的现象。首先，我们利用两种抗I类mAb（IgG 1同种型的6A 4和IgM同种型的A6-136），其已显示通过第1组和第2组NK克隆诱导受保护的靶细胞的裂解。添加用作F（ab '）（2）mAb的A6-136或6A 4导致通过所有分析的NK克隆裂解受保护的靶细胞。靶细胞由一组HLA纯合EB病毒转化的α细胞系（B-EBV）代表，而NK克隆代表显示不同GL 183/EB 6表面表型和/或不同裂解同种异体细胞能力的克隆。针对由植物血凝素诱导的母细胞或B-EBV转化的细胞系代表的自体靶细胞测试源自七个不同个体的未选择的NK克隆。在这两种情况下，添加6A 4 F（ab '）（2）和A6-136 mAb的混合物导致自体靶细胞的裂解，从而表明I类分子防止自体NK细胞对正常细胞的裂解。我们进一步研究了I类介导的保护是否需要I类分子的复合形式C1 R（Cw 4（+））靶细胞或81.22（Cw 3（+），Cw 4（+））在pH 2.2下的酸处理导致与6A 4的反应性丧失，A6-136和W 6 -32 mAb（已知与I类分子的组装形式反应）以及与L31 mAb（对HLA-C游离链具有特异性）的从头反应性。虽然未处理的Cw 4（+）C1 R细胞对Cw 4特异性组1 NK克隆的裂解具有抗性，但pH 2.2处理的细胞变得对相同克隆的裂解高度敏感。这些数据表明，至少对于所分析的NK克隆，靶细胞的保护需要复合形式的I类分子。
Some HLA-C alleles have been shown to exert a specific protective effect preventing target cells from lysis by groups of natural killer (NK) clones displaying a defined specificity. In this study, we analyzed whether class I-mediated protection is a more general phenomenon involving ail NK cells. First, we utilized two anti-class I mAbs (6A4 of IgG1 isotype and A6-136 of IgM isotype), which had been shown to induce lysis of protected target cells by group 1 and group 2 NK clones, Addition of A6-136 or 6A4 used as F(ab')(2) mAb resulted in lysis of protected target cells by all NK clones analyzed. Target cells were represented by a panel of HLA homozygous Epstein-Barr virus-transformed a cell lines (B-EBV) while NK clones were representative of clones displaying different GL183/EB6 surface phenotypes and/or different abilities to lyse allogeneic cells, Unselected NK clones derived from seven different individuals were tested against autologous target cells represented by phytohemagglutinin-induced blasts or B-EBV transformed cell lines, In both instances, addition of a mixture of 6A4 F(ab')(2) and A6-136 mAbs resulted in lysis of autologous target cells, thus suggesting that class I molecules prevent lysis of normal cells by self NK cells, We further investigated whether the class I-mediated protection requires the complexed form of class I molecules (composed of alpha chain, beta(2)-microglobulin and the antigen peptide) or rather the free alpha chain, Acidic treatment of the C1R (Cw4(+)) target cells or 81.22 (Cw3(+), Cw4(+)) at pH 2.2 resulted in loss of reactivity with 6A4, A6-136 and W6-32 mAb (known to react with the assembled form of class I molecules) and in the de novo reactivity with L31 mAb (specific for the HLA-C free chain). While the untreated Cw4(+) C1R cells were resistant to lysis by the Cw4-specific group 1 NK clones, the pH 2.2-treated cells became highly susceptible to lysis by the same clones. These data indicate that, at least for the NK clones analyzed, the protection of target cells requires class I molecules in the complexed form.