The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E residues
The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E residues
复制标题
DOI：
10.1002/eji.200324432
复制
发表时间：
2004-01-01
影响因子：
5.4
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
--
作者：
Wada, H;Matsumoto, N;Yamamoto, K
人类非经典MHC I类分子HLA-E是抑制性NK细胞受体（CD 94/NKG 2A）和活化性受体（CD 94/NKG 2d）的配体。为了鉴定被两种受体识别的HLA-E表面，特别是为了确定两种受体是否识别相同的表位，我们制备了一系列单独的Ala取代的HLA-E蛋白，并分析了它们与CD 94/NKG 2A或CD 94/NKG 2C的结合。8个显著损害HLA-E与CD 94/NKG 2A结合的HLA-E突变均位于HLA-E的α 1/α 2结构域的顶部。这些结果表明，CD 94/NKG 2A结合的HLA-E表面等同于云母上的NKG 2D结合位点。在损害HLA-E与CD 94/NKG 2A结合的8个突变中，6个显著损害HLA-E与CD 94/NKG 2C结合，表明CD 94/NKG 2C也结合HLA-E的类似表面。出乎意料的是，两个HLA-E突变（D 69 A和H155 A）选择性地消除了HLA-E与CD 94/NKG 2A的结合，而对CD 94/NKG 2C没有很大影响。这些结果表明，一个大部分共享，但部分不同的HLA-E残基组是由两个受体区分。
The human non-classical MHC class I molecule HLA-E is a ligand for both an inhibitory NK cell receptor (CD94/NKG2A) and an activating receptor (CD94/NKG2d). To identify HLA-E surface recognized by both receptors, especially to determine if both receptors recognize the same epitope, we made a series of individually Ala-substituted HLA-E proteins and analyzed their binding to CD94/NKG2A or CD94/NKG2C. Eight HLA-E mutations that significantly impaired HLA-E binding to CD94/NKG2A are all found in the top of alpha1/alpha2 domain of HLA-E. These results suggest that CD94/NKG2A binds a HLA-E surface equivalent to a NKG2D binding site on MICA. Of the eight mutations that impaired HLA-E binding to CD94/ NKG2A, six significantly impaired HLA-E binding to CD94/NKG2C suggesting that CD94/ NKG2C also binds a similar surface of HLA-E. Unexpectedly, the two HLA-E mutations (D69A and H155A) selectively abrogated HLA-E binding to CD94/NKG2A, not largely affected CD94/NKG2C. These results indicate that a mostly shared, but partly distinct set of HLA-E residues is discriminated by the two receptors.