A species-specific determinant on β2-microglobulin required for Ly49A recognition of its MHC class I ligand
A species-specific determinant on β2-microglobulin required for Ly49A recognition of its MHC class I ligand
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DOI：
10.1093/intimm/dxh017
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
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作者：
Mitsuki, M;Matsumoto, N;Yamamoto, K
小鼠抑制性 NK 细胞受体 Ly49A 识别小鼠 MHC I 类分子 H-2D(k)。本研究重点关注 Ly49A 和 H-2D(k) 之间相互作用中 MHC I 类不变成分 β(2)-微球蛋白 (β(2)m) 的物种特异性。用人(h) beta(2)m 转染β(2)m 缺陷型小鼠细胞系R1E/TL8x.1 诱导H-2D(k) 的细胞表面表达，但未能保护细胞免遭Ly49A(+) NK 细胞的杀伤。相反，用小鼠(m) beta(2)m转染的细胞免受Ly49A(+) NK细胞的杀伤。这些数据表明，Ly49A 在识别 H-2D(k) 复合物时可区分 mbeta(2)m 和 hbeta(2)m。为了确定 Ly49A 识别 H-2D(k) 所需的 beta(2)m 物种特异性决定簇，我们制备了一组 mbeta(2)m 突变体，并测试了包含每个 beta(2)m 突变体的 H-2D(k) 与 NK 细胞上的 Ly49A 结合的能力。 Ly49A 无法在功能上识别包含带有 K3R 和 Q29G 突变的 mbeta(2)m 的 H-2D(k)。此外，Ly49A 能够识别包含具有 R3K 和 G29Q 突变的 hbeta(2)m 的 H-2D(k)。这些数据表明 Lys3 和 Gln29 包含 Ly49A 识别 H-2D(k) 所需的物种特异性 β(2)m 决定簇的中心部分。这两个残基在小鼠和大鼠中是保守的，其中 NK 细胞使用 Ly49 家族分子作为 I 类 MHC 特异性受体。这些结果表明 β(2)m 在 NK 细胞识别靶细胞中的功能重要性。
The mouse inhibitory NK cell receptor Ly49A recognizes the mouse MHC class I molecule H-2D(k). The present study focuses on the species specificity of beta(2)-microglobulin (beta(2)m), an invariant component of MHC class I, in the interaction between Ly49A and H-2D(k). Transfection of the beta(2)m-defective mouse cell line R1E/TL8x.1 with human (h) beta(2)m induced cell-surface expression of H-2D(k), but failed to protect the cells from killing by Ly49A(+) NK cells. In contrast, the cells transfected with mouse (m) beta(2)m were protected from killing by Ly49A(+) NK cells. These data indicate that Ly49A distinguishes mbeta(2)m from hbeta(2)m when it recognizes the H-2D(k) complexes. To identify the species-specific determinant of beta(2)m required for Ly49A recognition of H-2D(k), we prepared a panel of mbeta(2)m mutants and tested the H-2D(k) that included each of the beta(2)m mutants for its capacity to engage Ly49A on NK cells. Ly49A failed to functionally recognize the H-2D(k) that included the mbeta(2)m with K3R and Q29G mutations. Moreover, Ly49A was able to recognize the H-2D(k) that included the hbeta(2)m with R3K and G29Q mutations. These data indicate that Lys3 and Gln29 consist of the central part of the species-specific determinant of beta(2)m required for Ly49A recognition of H-2D(k). The two residues are conserved in the mouse and the rat, in which NK cells use Ly49 family molecules as the receptors specific for MHC class I. These results suggest functional importance of beta(2)m in NK cell recognition of target cells.