Lee N, Llano M, Carretero M, Ishitani A, Navarro F, López-Botet M, Geraghty D E
The Clinical Research Division, Fred Hutchinson Cancer Research Center, 1124 Columbia St., M374, Seattle, WA 98104-2092, USA.
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5199-204. doi: 10.1073/pnas.95.9.5199.
We previously showed that the availability of a nonamer peptide derived from certain HLA class I signal sequences is a necessary requirement for the stabilization of endogenous HLA-E expression on the surface of 721.221 cells. This led us to examine the ability of HLA-E to protect HLA class I transfectants from natural killer (NK) cell-mediated lysis. It was possible to implicate the CD94/NKG2A complex as an inhibitory receptor recognizing this class Ib molecule by using as target a .221 transfectant selectively expressing surface HLA-E. HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1. Further studies of CD94/NKG2+ NK cell-mediated recognition of .221 cells transfected with different HLA class I allotypes (i.e., -Cw4, -Cw3, -B7) confirmed that the inhibitory interaction was mediated by CD94/NKG2A recognizing the surface HLA-E molecule, because only antibodies directed against either HLA-E, CD94, or CD94/NKG2A specifically restored lysis. Surface stabilization of HLA-E in cold-treated .221 cells loaded with appropriate peptides was sufficient to confer protection, resulting from recognition of the HLA class Ib molecule by the CD94/NKG2A inhibitory receptor. Consistent with the prediction that the ligand for CD94/NKG2A is expressed ubiquitously, our examination of HLA-E antigen distribution indicated that it is detectable on the surface of a wide variety of cell types.
我们之前的研究表明，源自某些HLA I类信号序列的九聚体肽的可用性是721.221细胞表面内源性HLA-E表达稳定的必要条件。这促使我们研究HLA-E保护HLA I类转染细胞免受自然杀伤（NK）细胞介导的裂解的能力。通过使用选择性表达表面HLA-E的.221转染细胞作为靶标，有可能将CD94/NKG2A复合物作为识别这种Ib类分子的抑制性受体。HLA-E通过已鉴定的免疫球蛋白超家族（Ig-SF）人类杀伤细胞抑制性受体或ILT2/LIR1没有明显的抑制作用。对CD94/NKG2+NK细胞介导的对转染了不同HLA I类同种异型（即-Cw4、-Cw3、-B七）的.221细胞的识别的进一步研究证实，抑制性相互作用是由识别表面HLA-E分子的CD94/NKG2A介导的，因为只有针对HLA-E、CD94或CD94/NKG2A的抗体才能特异性恢复裂解。在加载适当肽的冷处理.221细胞中HLA-E的表面稳定足以赋予保护作用，这是由于CD94/NKG2A抑制性受体识别了HLA Ib类分子。与CD94/NKG2A的配体普遍表达的预测一致，我们对HLA-E抗原分布的检查表明，它在多种细胞类型的表面均可检测到。
