Cannon John P, Haire Robert N, Magis Andrew T, Eason Donna D, Winfrey Kelley N, Hernandez Prada Jose A, Bailey Kate M, Jakoncic Jean, Litman Gary W, Ostrov David A
Department of Pediatrics, University of South Florida College of Medicine, St. Petersburg, FL 33701, USA.
Immunity. 2008 Aug 15;29(2):228-37. doi: 10.1016/j.immuni.2008.05.018. Epub 2008 Jul 31.
Novel immune-type receptors (NITRs) comprise an exceptionally large, diversified family of activating and inhibitory receptors that has been identified in bony fish. Here, we characterized the structure of an activating NITR that is expressed by a cytotoxic natural killer (NK)-like cell line and that specifically binds an allogeneic B cell target. A single amino acid residue within the NITR immunoglobulin variable (V)-type domain accounts for specificity of the interaction. Structures solved by X-ray crystallography revealed that the V-type domains of NITRs form homodimers resembling rearranging antigen-binding receptor heterodimers. CDR1 elements of both subunits of NITR dimers form ligand-binding surfaces that determine specificity for the nonself target. In the evolution of immune function, it appears that a specific NK type of innate recognition may be mediated by a complex germline multigene family of V structures resembling those that are somatically diversified in adaptive immunological responses.
新型免疫型受体（NITRs）构成了一个异常庞大且多样化的激活和抑制性受体家族，该家族已在硬骨鱼中被鉴定出来。在此，我们表征了一种激活型NITR的结构，该NITR由细胞毒性自然杀伤（NK）样细胞系表达，并特异性结合同种异体B细胞靶标。NITR免疫球蛋白可变（V）型结构域内的单个氨基酸残基决定了相互作用的特异性。通过X射线晶体学解析的结构表明，NITRs的V型结构域形成同型二聚体，类似于重排抗原结合受体异二聚体。NITR二聚体两个亚基的互补决定区1（CDR1）元件形成配体结合表面，决定了对非自身靶标的特异性。在免疫功能的进化过程中，似乎一种特定的NK型先天识别可能由一个复杂的种系多基因家族介导，该家族的V结构类似于在适应性免疫反应中发生体细胞多样化的那些结构。
