Fan Q R, Long E O, Wiley D C
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Nat Immunol. 2001 May;2(5):452-60. doi: 10.1038/87766.
Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits charge and shape complementarity. Specificity is mediated by a pocket in KIR2DL1 that hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids that differ between human and chimpanzee KIRs with HLA-C specificities form solvent-accessible clusters outside the KIR-HLA interface, which suggests undiscovered interactions by KIRs.
抑制性自然杀伤（NK）细胞受体在识别靶细胞上特定的I类主要组织相容性复合体（MHC）分子后会下调NK细胞的细胞毒性。我们在此报告了与I类MHC配体HLA-Cw4结合的抑制性人类杀伤细胞免疫球蛋白样受体2DL1（KIR2DL1）的晶体结构。KIR2DL1-HLA-Cw4界面表现出电荷和形状互补性。特异性由KIR2DL1中的一个口袋介导，该口袋容纳HLA-Cw4的Lys80残基。HLA-C和KIR2DL受体中保守的许多残基在KIR2DL1-HLA-Cw4和先前报道的KIR2DL2-HLA-Cw3复合物中形成不同的相互作用。在一个KIR2DL1-HLA-Cw4晶体中观察到了KIR-HLA-C复合物的二聚体聚集体。人类和黑猩猩具有HLA-C特异性的KIR之间不同的大多数氨基酸在KIR-HLA界面之外形成溶剂可及的簇，这表明KIR存在未被发现的相互作用。
