Coevolution of killer cell Ig-like receptors with HLA-C to become the major variable regulators of human NK cells.
Coevolution of killer cell Ig-like receptors with HLA-C to become the major variable regulators of human NK cells.
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DOI：
10.4049/jimmunol.1001494
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发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Parham P
中科院分区：
文献类型：
--
作者：
Older Aguilar AM;Guethlein LA;Adams EJ;Abi-Rached L;Moesta AK;Parham P
人类白细胞抗原I类分子和杀伤细胞免疫球蛋白样受体(KIR)之间的相互作用使人类NK细胞反应多样化。主要的KIR配体是MHC-C的C1和C2表位，这是一个仅限于人类和类人猿的年轻基因座。C1KIR和C1KIR最先进化，存在于猩猩身上，在功能上与人类的同类相似。猩猩缺乏C2和C2特异性的KIR，但具有独特的C1+C2特异性KIR，它与C1和C2同等结合。这种受体很可能是C2-KIR相互作用从C1-KIR进化而来的机制，同时避免了无功能的中间产物：孤儿受体或配体。与人激活KIR的选择性衰减相比，猩猩抑制MHC-C反应性KIR对具有相同亲和力和特异性的激活受体。猩猩C1KIR与人KIR识别的所有四个多态表位(C1、C2、Bw4和A3/11)发生反应或交叉反应，揭示了它们的结构共性。特异性决定位44处的饱和突变表明，KIR天生仅限于与这四个表位结合，无论是单独结合还是组合结合。这一限制使大多数人类白细胞抗原-A和-B变异体成为专用的T细胞受体配体，不会受到来自免疫反应的NK细胞和T细胞臂的相互冲突的压力。
Interactions between HLA class I and killer cell immunoglobulin-like receptors (KIR) diversify human NK cell responses. Dominant KIR ligands are the C1 and C2 epitopes of MHC-C, a young locus restricted to humans and great apes. C1 and C1-specific KIR evolved first, being present in orangutan and functionally like their human counterparts. Orangutans lack C2 and C2-specific KIR, but have a unique C1+C2 specific KIR that binds equally to C1 and C2. Such a receptor was likely the mechanism by which C2-KIR interaction evolved from C1-KIR while avoiding a non-functional intermediate: either orphan receptor or ligand. Orangutan inhibitory MHC-C reactive KIR pair with activating receptors of identical avidity and specificity, contrasting with the selective attenuation of human activating KIR. The orangutan C1-specific KIR reacts or cross-reacts with all four polymorphic epitopes (C1, C2, Bw4, and A3/11) recognized by human KIR, revealing their structural commonality. Saturation mutagenesis at specificity-determining position 44, demonstrates that KIR are inherently restricted to binding just these four epitopes, either individually or in combination. This restriction frees the majority of HLA-A and –B variants to be dedicated T-cell receptor ligands, not subject to conflicting pressures from the NK cell and T cell arms of the immune response.
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影响因子：
4.5
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
通讯作者：
Walter L
影响因子：
20.3
作者：
Andersson, Sandra;Fauriat, Cyril;Malmberg, Karl-Johan
通讯作者：
Malmberg, Karl-Johan
影响因子：
15.3
作者：
Barber, LD;Percival, L;Parham, P
通讯作者：
Parham, P
影响因子：
3.2
作者：
BRODSKY, FM;PARHAM, P
通讯作者：
PARHAM, P
影响因子：
5.4
作者：
Biassoni, R;Pessino, A;Moretta, A
通讯作者：
Moretta, A