HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A
HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A
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DOI：
10.1073/pnas.95.9.5199
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发表时间：
1998-04-28
影响因子：
11.1
通讯作者：
Geraghty, DE
中科院分区：
文献类型：
--
作者：
Lee, N;Llano, M;Geraghty, DE
我们先前的研究表明，获得来源于某些人类白细胞抗原I类信号序列的九聚体是稳定721.221细胞表面内源性人类白细胞抗原-E表达的必要条件。这使得我们检测了人类白细胞抗原-E保护人类白细胞抗原I类转染者免受自然杀伤(NK)细胞介导的裂解的能力，有可能通过以选择性表达表面人类白细胞抗原-E的.221转染体为靶点，暗示CD94/NKG2A复合体是识别这种Ib类分子的抑制性受体。CD94/NKG2+NK细胞对转入不同HLAI类异型(-Cw4、-Cw3、-B7)的0.221细胞的识别进一步研究证实，这种抑制作用是由CD94/NKG2A识别表面HLAE分子所介导的，因为只有针对HLAE、CD94或CD94/NKG2A的抗体才能特异性地恢复裂解，在负载适当多肽的冷处理.221细胞中，HLAE的表面稳定足以提供保护，这是由于CD94/NKG2A抑制受体识别HLAIb类分子所致。与CD94/NKG2A的配体普遍表达的预测一致，我们对HLA-E抗原分布的检测表明，它可在多种细胞类型的表面检测到。
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.