Bartel Yvonne, Bauer Björn, Steinle Alexander
Institute for Molecular Medicine, Goethe-University Frankfurt am Main , Frankfurt am Main , Germany.
Front Immunol. 2013 Nov 7;4:362. doi: 10.3389/fimmu.2013.00362.
Functional responses of natural killer (NK) cells including eradication of "harmful" cells and modulation of immune responses are regulated by a broad variety of activating and inhibitory NK receptors. Whereas the leukocyte receptor complex (LRC) encodes for NK receptors of the immunoglobulin superfamily, genes of C-type lectin-like NK receptors are clustered in the mammalian natural killer gene complex (NKC). Besides the thoroughly studied C-type lectin-like receptors NKG2D, CD94/NKG2x, and members of the murine Ly49 subfamily, the NKC also encodes for NK receptors of the less characterized NKRP1 subfamily. The prototypic mouse NKRP1 receptor is Nkrp1c (also known as NK1.1), while human members of the NKRP1 subfamily are NKRP1A, NKp80, and NKp65. The latter are not straight homologs of mouse NKRP1 receptors, but share distinct subfamily-specific traits classifying them as members of the NKRP1 subfamily. Ligands of the human NKPR1 receptors are likewise C-type lectin-like glycoproteins belonging to the CLEC2 subfamily (i.e., LLT1, AICL, and KACL), and are encoded in the NKC in tight genetic linkage to their respective receptors. Similarly, certain members of the mouse NKRP1 subfamily interact with genetically coupled CLEC2 glycoproteins, while the reasons for this intriguing tight genetic linkage remain unknown. Recent studies provided new and unique insights into the expression, interaction, and signaling of NKRP1 receptors and their ligands, thereby substantially advancing our understanding of their function and biology. Here, we review our current knowledge on NKRP1 receptors and their genetically linked CLEC2 ligands with an emphasis on the human receptor/ligand pairs NKRP1A-LLT1, NKp80-AICL, and NKp65-KACL.
自然杀伤（NK）细胞的功能反应，包括清除“有害”细胞和调节免疫反应，受多种激活和抑制性NK受体调控。白细胞受体复合物（LRC）编码免疫球蛋白超家族的NK受体，而C型凝集素样NK受体的基因则聚集在哺乳动物自然杀伤基因复合体（NKC）中。除了深入研究的C型凝集素样受体NKG2D、CD94/NKG2x以及小鼠Ly49亚家族成员外，NKC还编码特征较少的NKRP1亚家族的NK受体。小鼠NKRP1受体的原型是Nkrp1c（也称为NK1.1），而NKRP1亚家族的人类成员是NKRP1A、NKp80和NKp65。后者并非小鼠NKRP1受体的直系同源物，但具有独特的亚家族特异性特征，将它们归类为NKRP1亚家族成员。人类NKPR1受体的配体同样是属于CLEC2亚家族的C型凝集素样糖蛋白（即LLT1、AICL和KACL），并在NKC中与其各自的受体紧密连锁编码。同样，小鼠NKRP1亚家族的某些成员与基因偶联的CLEC2糖蛋白相互作用，而这种有趣的紧密基因连锁的原因仍然未知。最近的研究为NKRP1受体及其配体的表达、相互作用和信号传导提供了新的独特见解，从而极大地推进了我们对其功能和生物学的理解。在此，我们综述了目前关于NKRP1受体及其基因连锁的CLEC2配体的知识，重点关注人类受体/配体对NKRP1A - LLT1、NKp80 - AICL和NKp65 - KACL。
