Humans differ from other hominids in lacking an activating NK cell receptor that recognizes the C1 epitope of MHC class I.
Humans differ from other hominids in lacking an activating NK cell receptor that recognizes the C1 epitope of MHC class I.
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DOI：
10.4049/jimmunol.1001951
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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：
Moesta AK;Graef T;Abi-Rached L;Older Aguilar AM;Guethlein LA;Parham P
杀伤细胞免疫球蛋白样受体(KIR)和MHC-I类受体对人NK细胞功能的调节主要受抑制系III KIR与人类白细胞抗原C的C_1和C_2表位的两部分相互作用所支配。相比之下，激活谱系III KIR的配体特异性和功能贡献仍然知之甚少。使用一种可靠、灵敏的KIR结合分析和95个HLAI类靶点的代表性小组，我们发现KIR2DS1与C2与∼的亲和力是KIR2DL1的50%，而KIR2DS2、2DS3和2DS5对C1、C2或任何其他HLAI类表位没有可检测到的亲和力。相比之下，黑猩猩具有激活C1和C2特异性谱系III KIR的强大亲和力，与它们配对的抑制性受体的亲和力相当。黑猩猩Pt-KIR3DS2的一个变体，激活C2特异性受体，对C2的亲和力与抑制性铂-KIR3DL4相同，第二个变体的亲和力为∼的73%。黑猩猩Pt-KIR3DS6是一种激活的c1受体，其对c1的亲和力是抑制性的pT-kIR2DL6的70%∼。在人类和黑猩猩中，我们都观察到了一种进化趋势，即通过选择性地获取衰减性替代来降低激活的C1和C2特异性受体的亲和力。然而，人类的衰减程度是极端的，KIR2DS2就是一个例子，它是一种激活的C1特异性受体，已经失去了对HLAI类的所有可检测的亲和力。支持这种消除激活的C1特异性受体是因为大猩猩中存在激活C1特异性受体(Gogo-KIR2DSa)的高亲和力。
Modulation of human NK cell function by killer cell immunoglobulin-like receptors (KIR) and MHC class I is dominated by the bipartite interactions of inhibitory lineage III KIR with the C1 and C2 epitopes of HLA-C. In comparison, the ligand specificities and functional contributions of the activating lineage III KIR remain poorly understood. Using a robust, sensitive assay of KIR binding and a representative panel of 95 HLA class I targets, we show that KIR2DS1 binds C2 with ∼50% the avidity of KIR2DL1, whereas KIR2DS2, 2DS3 and 2DS5 have no detectable avidity for C1, C2 or any other HLA class I epitope. In contrast, the chimpanzee has activating C1 and C2-specific lineage III KIR with strong avidity, comparable to those of their paired inhibitory receptors. One variant of chimpanzee Pt-KIR3DS2, the activating C2-specific receptor, has the same avidity for C2 as inhibitory Pt-KIR3DL4, and a second variant has ∼73% the avidity. Chimpanzee Pt-KIR3DS6, the activating C1-specific receptor, has avidity for C1 that is ∼70% that of inhibitory Pt-KIR2DL6. In both humans and chimpanzees we observe an evolutionary trend toward reducing the avidity of the activating C1- and C2-specific receptors through selective acquisition of attenuating substitutions. However, the extent of attenuation has been extreme in humans as exemplified by KIR2DS2, an activating C1-specific receptor that has lost all detectable avidity for HLA class I. Supporting such elimination of activating C1-specific receptors as a uniquely human phenomenon is the presence of a high avidity activating C1-specific receptor (Gogo-KIR2DSa) in gorilla.
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DOI：
10.4049/jimmunol.1001494
发表时间：
2010-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Older Aguilar AM;Guethlein LA;Adams EJ;Abi-Rached L;Moesta AK;Parham P
通讯作者：
Parham P
DOI：
10.1073/pnas.95.24.14326
发表时间：
1998-11-24
影响因子：
11.1
作者：
Valés-Gómez, M;Reyburn, HT;Strominger, J
通讯作者：
Strominger, J
影响因子：
32.4
作者：
Khakoo, SI;Rajalingam, R;Parham, P
通讯作者：
Parham, P
影响因子：
5
作者：
VandenBussche, C. J.;Mulrooney, T. J.;Frazier, W. R.;Dakshanamurthy, S.;Hurley, C. K.
通讯作者：
Hurley, C. K.
影响因子：
20.3
作者：
Yawata, Makoto;Yawata, Nobuyo;Parham, Peter
通讯作者：
Parham, Peter