Structural requirements for the activation of vomeronasal sensory neurons by MHC peptides
Structural requirements for the activation of vomeronasal sensory neurons by MHC peptides
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DOI：
10.1038/nn.2452
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发表时间：
2009-12-01
影响因子：
25
通讯作者：
Boehm, Thomas
中科院分区：
文献类型：
--
作者：
Leinders-Zufall, Trese;Ishii, Tomohiro;Boehm, Thomas
除了它们在免疫应答中的作用之外，主要组织相容性复合物（MHC）分子的肽配体还作为哺乳动物鼻中犁鼻感觉神经元（VSN）亚群的嗅觉线索起作用。这些细胞如何识别和编码MHC肽的多样性尚不清楚。我们发现，小鼠VSN表达犁鼻受体基因V2 r1 b（也称为Vmn 2 r26）检测MHC肽在亚皮摩尔浓度，并表现出重叠特异性的组合激活。在给定的细胞中，肽的反应性是广泛的，但高度特异性;可以区分由单个氨基酸残基不同的肽。转录V2 r1 b基因座的细胞已被基因靶向破坏，不再显示这种肽反应。我们的研究结果揭示了VSN对MHC肽的反应的基本参数。我们认为MHC分子提供的肽呈递系统与T细胞和VSN表达的肽识别系统共同进化。
In addition to their role in the immune response, peptide ligands of major histocompatibility complex (MHC) molecules function as olfactory cues for subsets of vomeronasal sensory neurons (VSNs) in the mammalian nose. How MHC peptide diversity is recognized and encoded by these cells is unclear. We found that mouse VSNs expressing the vomeronasal receptor gene V2r1b (also known as Vmn2r26) detected MHC peptides at subpicomolar concentrations and exhibited combinatorial activation with overlapping specificities. In a given cell, peptide responsiveness was broad, but highly specific; peptides differing by a single amino-acid residue could be distinguished. Cells transcribing a V2r1b locus that has been disrupted by gene targeting no longer showed such peptide responses. Our results reveal fundamental parameters governing the response to MHC peptides by VSNs. We suggest that the peptide presentation system provided by MHC molecules co-evolves with the peptide recognition systems expressed by T cells and VSNs.