Franksson L, Sundbäck J, Achour A, Bernlind J, Glas R, Kärre K
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Eur J Immunol. 1999 Sep;29(9):2748-58. doi: 10.1002/(SICI)1521-4141(199909)29:09<2748::AID-IMMU2748>3.0.CO;2-C.
MHC class I molecules can prevent NK cell-mediated cytotoxicity by interacting with inhibitory receptors on the effector cells. Different conclusions have been reached regarding possible peptide selectivity of these receptors. To address whether peptide selectivity is an exclusive feature of human or immunoglobulin-superfamily receptors, we have studied a system based on the murine NK receptor Ly-49C in the lectin-superfamily. Loading of TAP-deficient RMA-S cells with the H-2Kb-restricted, ovalbumin-derived peptide OVA(257 - 264) (pOVA) induced their ability to bind Ly-49C-transfected reporter cells, and also protected them from killing by Ly-49C+ NK cells. Other peptides that bound and stabilized H-2Kb equally well differed in their NK protective capacity. Comparison of the MHC class I peptide complexes (crystal structures and molecular models) revealed a conformational motif encompassing the C-terminal parts of the alpha1 helix (73 - 77) and the bound peptide that was common for the protective complexes. Substitution analysis of pOVA suggested that position 7 in the peptide may be critical for optimal protection as well as for the conformational motif at position 73 - 77. In conclusion, protection mediated by the murine C-type lectin receptor Ly-49C is peptide dependent and selective.
MHC I类分子可通过与效应细胞上的抑制性受体相互作用来阻止NK细胞介导的细胞毒性。关于这些受体可能的肽选择性，已经得出了不同的结论。为了探讨肽选择性是否是人类或免疫球蛋白超家族受体的独特特征，我们研究了一个基于凝集素超家族中的小鼠NK受体Ly-49C的系统。用H-2Kb限制性的、卵清蛋白衍生的肽OVA(257 - 264)（pOVA）加载TAP缺陷的RMA-S细胞，诱导了它们与Ly-49C转染的报告细胞结合的能力，并且还保护它们免受Ly-49C+ NK细胞的杀伤。其他同样能很好地结合并稳定H-2Kb的肽，其NK保护能力有所不同。对MHC I类肽复合物（晶体结构和分子模型）的比较揭示了一种构象基序，该基序包含α1螺旋（73 - 77）的C末端部分以及保护性复合物共有的结合肽。pOVA的替代分析表明，肽中的第7位可能对最佳保护以及73 - 77位的构象基序至关重要。总之，小鼠C型凝集素受体Ly-49C介导的保护是肽依赖性和选择性的。
