Nonclassical HLA-G molecules are classical peptide presenters
Nonclassical HLA-G molecules are classical peptide presenters
复制标题
DOI：
10.1016/s0960-9822(02)00481-5
复制
发表时间：
1996-03-01
期刊：
影响因子：
9.2
通讯作者：
Rammensee, HG
中科院分区：
文献类型：
--
作者：
Diehl, M;Munz, C;Rammensee, HG
背景：经典HLA（人类白细胞抗原）分子HLA-A、HLA-B和HLA-C的生理功能是将肽呈递给T细胞并抑制自然杀伤细胞的活性，相反，非经典HLA分子，例如HLA-E、HLA-F和HLA-G的功能仍有待确定。 HLA-G 的表达很大程度上限于胎盘滋养层，它可能介导保护胎儿免受母亲排斥。通过有关 HLA-G 分子的生化特性的信息，尤其是其作为肽受体的潜在能力，应有助于实现了解 HLA-G 功能的目的。结果：为了研究 HLA-G 的肽呈递，我们使用稳定转染的 LCL721.221 细胞作为 HLA-G 的来源。 HLA-G 分子并通过个体测序和池测序分析提取的肽谱。我们的结果表明，HLA-G 分子与经典 HLA 分子一样，与多种源自细胞蛋白的肽相关。 HLA-G 呈递的肽通常由 9 个氨基酸组成，并附着在特定的序列基序上，锚定残基位于第 2 位（异亮氨酸或亮氨酸）、第 3 位（脯氨酸）和羧基端第 9 位（亮氨酸）。因此，HLA-G 肽配体基序遵循经典 HLA 基序的原理，尽管它显示出自己独特的特征，肽结合测定表明三个锚定残基中的两个足以结合，并且我们鉴定的三个天然 HLA-G 配体不仅与 HLA-G 结合，而且与 HLA-A2 结合。这并不奇怪，因为 HLA-A2 和 HLA-G 的结合口袋在识别位置 2 和 9 处的锚残基方面存在重叠。同样，一些（但不是全部）HLA A2 肽配体也可以与 HLA-G 结合。 结论：非经典 HLA-G 分子呈递肽的方式与经典 HLA 分子基本相同。我们确定了HLA-G特异性识别的肽基序；其基本特征由序列 XI/LPXXXXXL 描述。这些信息应该有助于阐明 HLA-G 分子在胎儿-母体界面的生理作用。最有可能的是，这种作用是保护胎儿细胞免遭自然杀伤细胞裂解，并可能将外源肽呈递给一类尚未鉴定的 T 细胞。
Background: The physiological functions of the classical HLA (human leukocyte antigen) molecules, HLA-A, HLA-B and HLA-C, are to present peptides to T cells and to inhibit the activity of natural killer cells, In contrast, the functions of nonclassical HLA-molecules, such as HLA-E, HLA-F and HLA-G, remain to be established. The expression of HLA-G is largely limited to the placental trophoblast, where it might mediate protection of the fetus from rejection by the mother, Achieving the aim of understanding the function of HLA-G should be facilitated by information on the biochemical properties of HLA-G molecules, especially on their potential ability to act as peptide receptors.Results: To study peptide presentation by HLA-G, we used stably transfected LCL721.221 cells as a source of HLA-G molecules and analysed the spectrum of extracted peptides by individual and pool sequencing. Our results indicate that HLA-G molecules, like classical HLA molecules, are associated with a wide array of peptides derived from cellular proteins. Peptides presented by HLA-G usually consisted of 9 amino acids, and adhered to a specific sequence motif, with anchor residues at position 2 (isoleucine or leucine), position 3 (proline) and the carboxy-terminal position 9 (leucine). Thus, the HLA-G peptide ligand motif follows the principles of classical HLA motifs, although it displays its own unique features, Peptide-binding assays indicated that two of the three anchor residues were sufficient for binding, and that the three natural HLA-G ligands that we identified bound, not only to HLA-G, but also to HLA-A2. This was not surprising, because the binding pockets of HLA-A2 and HLA-G overlap in their ability to recognize anchor residues at positions 2 and 9. Likewise, some, but not all, HLA A2 peptide ligands could also bind to HLA-G.Conclusions: Nonclassical HLA-G molecules present peptides essentially in the same way as classical HLA molecules do. We determined the peptide motif that is specifically recognized by HLA-G; its basic features are described by the sequence XI/LPXXXXXL. This information should help to elucidate the physiological role of HLA-G molecules at the fetal-maternal interface, Most likely, this role is to protect fetal cells from lysis by natural killer cells, and possibly to present foreign peptides to a class of T cells that has not yet been identified.