A novel system of polymorphic and diverse NK cell receptors in primates.
A novel system of polymorphic and diverse NK cell receptors in primates.
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DOI：
10.1371/journal.pgen.1000688
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发表时间：
2009-10
期刊：
影响因子：
4.5
通讯作者：
Walter L
中科院分区：
文献类型：
--
作者：
Averdam A;Petersen B;Rosner C;Neff J;Roos C;Eberle M;Aujard F;Münch C;Schempp W;Carrington M;Shiina T;Inoko H;Knaust F;Coggill P;Sehra H;Beck S;Abi-Rached L;Reinhardt R;Walter L
哺乳动物的自然杀伤（NK）细胞受体主要有两类：杀伤细胞免疫球蛋白样受体（KIR）和结构无关的杀伤细胞凝集素样受体（KLR）。虽然KIR代表了迄今为止研究的所有灵长类动物中最多样化的NK受体组，包括人类，类人猿和新旧世界猴子，但KLR代表了啮齿类动物的功能等同。在这里，我们报道了狐猴中这一规则的第一个离题，其中KLR （CD94/NKG2）而不是KIR构成了最多样化的NK细胞受体组。我们证明了自然选择促成了狐猴的这种多样化，特别是靶向KLR残基与MHC I类配体呈现的肽相互作用。我们进一步表明狐猴缺乏MHC-E的严格同源或功能等效物，MHC-E是“高等”灵长类动物中非多态性KLR的配体。我们的数据支持在灵长类动物中存在一个迄今为止未知的多态和多样化NK细胞受体系统，以及组合多样性作为增加NK细胞受体库的新机制。自然杀伤（NK）细胞的大多数受体与高度多态性的主要组织相容性复合体（MHC） I类分子相互作用，从而调节NK细胞对感染或恶性靶细胞的活性。人类、类人猿和新旧世界猴子使用杀伤细胞免疫球蛋白样受体家族（KIR）作为高度多样化的NK细胞受体，而啮齿动物则使用多种凝集素样受体家族Ly49来完成这一功能。这种功能分离是什么时候在进化中发生的？随后，我们调查了狐猴，一种与人类远亲的灵长类动物。我们在这里展示了狐猴使用CD94/NKG2家族作为其高度多样化的NK细胞受体。CD94/NKG2受体也属于凝集素样受体家族，但在“高等”灵长类动物和啮齿动物中相当保守。我们可以进一步证明狐猴像其他灵长类动物一样有一个Ly49基因，但缺乏KIR3DL谱系的功能性KIR基因，并且在它们的MHC I类基因组组织中显示出主要偏差。因此，狐猴进化出了“第三种方式”的多态和多样化NK细胞受体。此外，扩增后的狐猴CD94/NKG2受体可以自由结合，形成多种受体。因此，这是对NK细胞受体的一些组合多样性的首次描述。
There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of non-polymorphic KLR in “higher” primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire. Most receptors of natural killer (NK) cells interact with highly polymorphic major histocompatibility complex (MHC) class I molecules and thereby regulate the activity of NK cells against infected or malignant target cells. Whereas humans, apes, and Old and New World monkeys use the family of killer cell immunoglobulin-like receptors (KIR) as highly diverse NK cell receptors, this function is performed in rodents by the diverse family of lectin-like receptors Ly49. When did this functional separation occur in evolution? We followed this by investigating lemurs, primates that are distantly related to humans. We show here that lemurs employ the CD94/NKG2 family as their highly diversified NK cell receptors. The CD94/NKG2 receptors also belong to the lectin-like receptor family, but are rather conserved in “higher” primates and rodents. We could further demonstrate that lemurs have a single Ly49 gene like other primates but lack functional KIR genes of the KIR3DL lineage and show major deviations in their MHC class I genomic organisation. Thus, lemurs have evolved a “third way” of polymorphic and diverse NK cell receptors. In addition, the multiplied lemur CD94/NKG2 receptors can be freely combined, thereby forming diverse receptors. This is, therefore, the first description of some combinatorial diversity of NK cell receptors.
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影响因子：
7.8
作者：
Parham P
通讯作者：
Parham P
DOI：
10.1073/pnas.0802736105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Kaiser, Brett K.;Pizarro, Juan Carlos;Strong, Roland K.
通讯作者：
Strong, Roland K.
影响因子：
100.3
作者：
Eagle, Robert A.;Trowsdale, John
通讯作者：
Trowsdale, John
DOI：
10.1084/jem.20072525
发表时间：
2008-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Petrie EJ;Clements CS;Lin J;Sullivan LC;Johnson D;Huyton T;Heroux A;Hoare HL;Beddoe T;Reid HH;Wilce MC;Brooks AG;Rossjohn J
通讯作者：
Rossjohn J
影响因子：
5.4
作者：
Braud, V;Jones, EY;McMichael, A
通讯作者：
McMichael, A