MHC class I recognition by NK receptors in the Ly49 family is strongly influenced by the β2-microglobulin subunit
MHC class I recognition by NK receptors in the Ly49 family is strongly influenced by the β2-microglobulin subunit
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DOI：
10.4049/jimmunol.166.12.7327
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发表时间：
2001-06-15
影响因子：
4.4
通讯作者：
Kärre, K
中科院分区：
文献类型：
--
作者：
Michaëlsson, J;Achour, A;Kärre, K
NK细胞对目标的识别受到MHC I类特异性受体的强烈影响。最近发表的抑制受体Ly49A与H-2D复合物的结构(d)揭示了晶体中两个不同的相互作用位点。其中之一涉及MHC I类复合体的α(1)、α(2)、α(3)和β(2)-微球蛋白（β (2)m）结构域。来自该结构的数据，以及早期使用MHC I类四聚体研究的差异，促使我们研究β (2)m亚基在MHC I类ly49相互作用中的作用。在这里，据我们所知，我们提供了第一个直接证据，证明β (2)m亚基中的残基影响MHC I类分子与Ly49受体的结合。在三种不同的MHC I类分子H-2D(b)、H-2K(b)和H-2D(d)中，从小鼠β (2)m到人类β (2)m的变化导致与受体Ly49A和Ly49C的结合丧失。在已发表的晶体结构中，对Ly49A与H-2D(d)结合的氨基酸进行了分析，并在小鼠和人类β (2)m之间进行了不同的分析，表明由残基Lys(3)、Thr(4)、Thr（28）和Gln（29）组成的簇可能是Ly49A-H-2D(d)相互作用的重要结构域。另一种可能性是β (2)m的变化间接影响MHC I类分子远端部分的构象，包括重链的α和α(2)结构域。
NK cell recognition of targets is strongly affected by MHC class I specific receptors. The recently published structure of the inhibitory receptor Ly49A in complex with H-2D(d) revealed two distinct sites of interaction in the crystal. One of these involves the alpha (1), alpha (2), alpha (3), and beta (2)-microglobulin (beta (2)m) domains of the MHC class I complex. The data from the structure, together with discrepancies in earlier studies using MHC class I tetramers, prompted us to study the role of the beta (2)m subunit in MHC class I-Ly49 interactions. Here we provide, to our knowledge, the first direct evidence that residues in the beta (2)m subunit affect binding of MHC class I molecules to Ly49 receptors. A change from murine beta (2)m to human beta (2)m in three different MHC class I molecules, H-2D(b), H-2K(b), and H-2D(d), resulted in a loss of binding to the receptors Ly49A and Ly49C. Analysis of the amino acids involved in the binding of Ly49A to H-2D(d) in the published crystal structure, and differing between the mouse and the human beta (2)m, suggests the cluster formed by residues Lys(3), Thr(4), Thr(28), and Gln(29), as a potentially important domain for the Ly49A-H-2D(d) interaction. Another possibility is that the change of beta (2)m indirectly affects the conformation of distal parts of the MHC class I molecule, including the alpha, and alpha (2) domains of the heavy chain.