The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor.
The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor.
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DOI：
10.1084/jem.181.3.1133
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发表时间：
1995-03-01
期刊：
影响因子：
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通讯作者：
Parham P
中科院分区：
文献类型：
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作者：
Gumperz JE;Litwin V;Phillips JH;Lanier LL;Parham P
尽管靶细胞的I类HLA分子对自然杀伤（NK）细胞介导的溶解的抑制是一种既定现象，但对诱导这种效应的I类分子特征的了解仍然是初步的。使用I类等位基因HLA-B *1502和B*1513（它们仅在限定Bw 4和Bw 6血清学表位的残基77-83处不同），我们检验了I类分子上Bw 4表位的存在决定了NKB 1 + NK细胞的识别的假设。HLA- B*1513具有Bw 4表位，而B*1502具有Bw 6表位。表达B*1513作为唯一HLA-A、-B或-C分子的转染靶细胞的NKB 1 + NK细胞克隆的裂解被抑制，而表达B*1502的转染子的杀伤则没有。添加抗NKB 1单克隆抗体重建了表达B*1513的靶标的裂解，但不影响对携带B*1502的靶标的杀伤。B*1513的抑制作用可通过加入抗I类单克隆抗体类似地防止。这些结果表明Bw 4表位的存在影响表达NKB 1的NK细胞对HLA-B分子的识别，并表明NKB 1分子可能作为Bw 4 + HLA-B等位基因的受体。Bw 4区域外的序列也一定会影响NKB 1 + NK细胞的识别，因为表达HLA-A*2403或A*2501的转染子的裂解不会因加入抗NKB 1抗体而增加，所述转染子具有Bw 4表位，但在其他方面与HLA-B分子实质上不同。天冬酰胺86是I类分子上N-连接糖基化的单一位点，与Bw 4/Bw 6区域非常接近。突变Bw 4阳性分子B*5801的糖基化位点，并测试突变分子对NKB 1 + NK细胞的抑制。观察到可通过添加抗NKB 1单克隆抗体逆转的抑制，表明碳水化合物部分的存在对于NKB 1 + NK细胞克隆的I类识别不是必需的。
Although inhibition of natural killer (NK) cell-mediated lysis by the class I HLA molecules of target cells is an established phenomenon, knowledge of the features of class I molecules which induce this effect remains rudimentary. Using class I alleles HLA-B*1502 and B*1513 which differ only at residues 77-83 which define the Bw4 and Bw6 serological epitopes, we tested the hypothesis that the presence of the Bw4 epitope on class I molecules determines recognition by NKB1+ NK cells. HLA- B*1513 possesses the Bw4 epitope, whereas B*1502 has the Bw6 epitope. Lysis by NKB1+ NK cell clones of transfected target cells expressing B*1513 as the only HLA-A, -B, or -C molecule was inhibited, whereas killing of transfectants expressing B*1502 was not. Addition of an an anti-NKB1 monoclonal antibody reconstituted lysis of the targets expressing B*1513, but did not affect killing of targets bearing B*1502. The inhibitory effect of B*1513 could be similarly prevented by the addition of an anti-class I monoclonal antibody. These results show that the presence of the Bw4 epitope influences recognition of HLA-B molecules by NK cells that express NKB1, and suggest that the NKB1 molecule may act as a receptor for Bw4+ HLA-B alleles. Sequences outside of the Bw4 region must also affect recognition by NKB1+ NK cells, because lysis of transfectants expressing HLA-A*2403 or A*2501, which possess the Bw4 epitope but are in other ways substantially different from HLA-B molecules, was not increased by addition of the anti-NKB1 antibody. Asparagine 86, the single site of N-linked glycosylation on class I molecules, is in close proximity to the Bw4/Bw6 region. The glycosylation site of the Bw4-positive molecule B*5801 was mutated, and the mutant molecules tested for inhibition of NKB1+ NK cells. Inhibition that could be reversed by addition of the anti-NKB1 monoclonal antibody was observed, showing the presence of the carbohydrate moiety is not essential for class I recognition by NKB1+ NK cell clones.