Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes
Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes
复制标题
DOI：
10.1073/pnas.0913108107
复制
发表时间：
2010-03-16
影响因子：
11.1
通讯作者：
Steinle, Alexander
中科院分区：
文献类型：
--
作者：
Spreu, Jessica;Kuttruff, Sabrina;Steinle, Alexander
许多众所周知的免疫相关的C型凝集素样受体（CTLR），如NKG 2D、CD 69和Ly 49受体，都编码在自然杀伤基因复合物（NKC）中。最近，我们表征了编码KACL的孤儿NKC基因CLEC 2A，KACL是CTLR的人CLEC 2家族的另一个成员。与其他CLEC 2家族成员AICL、CD 69和LLT 1相反，KACL表达主要限于皮肤。在这里，我们表明，KACL是一个非二硫键连接的同型二聚体表面受体，并刺激细胞毒性的人NK 92 MI细胞。我们确定了NK 92 MI细胞上相应的激活受体，其邻近CLEC 2A位点编码，并以高亲和力结合KACL。这种CTLR，称为NKp 65，刺激NK细胞毒性和促炎细胞因子的释放后，细胞结合的KACL的参与。NKp 65是人类活化NK受体NKp 80的远亲，具有NKp 65介导的细胞毒性所需的氨基末端半ITAM。最后，我们表明，KACL的表达主要限于角质形成细胞。新鲜分离的角质形成细胞表达KACL，并且能够以KACL依赖性方式刺激表达NKp 65的细胞。因此，我们报告了一种独特的NKC编码的受体-配体系统，该系统可能在人类皮肤的免疫生物学中发挥专门的功能。
Many well-known immune-related C-type lectin-like receptors (CTLRs) such as NKG2D, CD69, and the Ly49 receptors are encoded in the natural killer gene complex (NKC). Recently, we characterized the orphan NKC gene CLEC2A encoding for KACL, a further member of the human CLEC2 family of CTLRs. In contrast to the other CLEC2 family members AICL, CD69, and LLT1, KACL expression is mostly restricted to skin. Here we show that KACL is a non-disulfide-linked homodimeric surface receptor and stimulates cytotoxicity by human NK92MI cells. We identified the corresponding activating receptor on NK92MI cells that is encoded adjacently to the CLEC2A locus and binds KACL with high affinity. This CTLR, termed NKp65, stimulates NK cytotoxicity and release of proinflammatory cytokines upon engagement of cell-bound KACL. NKp65, a distant relative of the human activating NK receptor NKp80, possesses an amino-terminal hemITAM that is required for NKp65-mediated cytotoxicity. Finally, we show that KACL expression is mainly restricted to keratinocytes. Freshly isolated keratinocytes express KACL and are capable of stimulating NKp65-expressing cells in a KACL-dependent manner. Thus, we report a unique NKC-encoded receptor-ligand system that may fulfill a dedicated function in the immunobiology of human skin.