Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases/National Institutes of Health Rockville, MD, USA.
Front Immunol. 2012 Aug 20;3:258. doi: 10.3389/fimmu.2012.00258. eCollection 2012.
KIR2DL4 is an unusual killer cell immunoglobulin-like receptor (KIR) family member in terms of its structure, expression, cellular localization, and signaling properties. The most conserved KIR in evolution, it is referred to as a framework KIR gene and is expressed by all natural killer (NK) cells and a subset of T cells. Although it has a long cytoplasmic tail that is typical of inhibitory KIR, engagement of this receptor results in the activation of NK cells, not for cytotoxicity, but for cytokine and chemokine secretion. Unlike all other KIRs, which are expressed on the surface of NK cells, KIR2DL4 resides in endosomes. It signals from this intracellular site for a proinflammatory and proangiogenic response, using a novel endosomal signaling pathway that involves the serine/threonine kinases DNA-PKcs and Akt. The only known ligand of KIR2DL4 is HLA-G. Soluble HLA-G accumulates in KIR2DL4(+) endosomes. Unlike classical HLA molecules that serve as ligands for other KIR family members, in healthy individuals, HLA-G expression is restricted to the fetal trophoblast cells that invade the maternal decidua during early pregnancy. Since NK cells constitute the predominant lymphocyte subset at this site, the proinflammatory/proangiogenic outcome of the interaction between KIR2DL4 and soluble HLA-G supports a role for KIR2DL4 in the extensive remodeling of the maternal vasculature during the early weeks of pregnancy.
KIR2DL4 在结构、表达、细胞定位和信号转导特性方面是一种不寻常的杀伤细胞免疫球蛋白样受体 (KIR) 家族成员。作为进化中最保守的 KIR，它被称为框架 KIR 基因，由所有自然杀伤 (NK) 细胞和一部分 T 细胞表达。尽管它具有典型抑制性 KIR 的长胞质尾，但该受体的结合导致 NK 细胞的激活，而不是细胞毒性，而是细胞因子和趋化因子的分泌。与其他所有在 NK 细胞表面表达的 KIR 不同，KIR2DL4 位于内体中。它从这个细胞内位置发出信号，引发促炎和促血管生成反应，使用一种涉及丝氨酸/苏氨酸激酶 DNA-PKcs 和 Akt 的新型内体信号通路。KIR2DL4 的唯一已知配体是 HLA-G。可溶性 HLA-G 在 KIR2DL4(+)内体中积累。与作为其他 KIR 家族成员配体的经典 HLA 分子不同，在健康个体中，HLA-G 的表达仅限于在妊娠早期侵袭母体蜕膜的胎儿滋养层细胞。由于 NK 细胞是该部位主要的淋巴细胞亚群，因此 KIR2DL4 与可溶性 HLA-G 之间相互作用的促炎/促血管生成结果支持 KIR2DL4 在妊娠早期母体血管广泛重塑中的作用。
