ALTERED PHENOTYPE AND FUNCTION OF NATURAL-KILLER-CELLS EXPRESSING THE MAJOR HISTOCOMPATIBILITY COMPLEX RECEPTOR LY-49 IN MICE TRANSGENIC FOR ITS LIGAND
ALTERED PHENOTYPE AND FUNCTION OF NATURAL-KILLER-CELLS EXPRESSING THE MAJOR HISTOCOMPATIBILITY COMPLEX RECEPTOR LY-49 IN MICE TRANSGENIC FOR ITS LIGAND
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DOI：
10.1073/pnas.92.5.1649
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发表时间：
1995-02-28
影响因子：
11.1
通讯作者：
SENTMAN, CL
中科院分区：
文献类型：
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作者：
OLSSON, MY;KARRE, K;SENTMAN, CL
已经显示Ly-49分子与主要组织相容性复合体（MHC）I类分子相互作用，并且来自C57 BL/（6）（H-2（B））小鼠的Ly-49（+）自然杀伤（NK）细胞的溶解功能被肿瘤靶细胞上的H-2D（d）识别所抑制。C57 BL/6小鼠体内的Ly-49（+）NK细胞的百分比（13-18%）没有改变，但它对该亚群产生了三种功能效应。(i)与C57 BL/6对照小鼠相比，阳性群体中的Ly-49表达降低了30-50%。（ii）虽然转基因小鼠中的该Ly-49（+）亚群（Ly-49 lo）未能杀死具有高H-2D（d）表达的BALB/c伴刀豆球蛋白A（Con A）母细胞，但它能够杀死具有低H-2D（d）表达的SP2/O肿瘤细胞。来自非转基因小鼠的Ly-49（+）NK细胞（Ly-49 hi）不能杀死这两种表达H-2D（d）的靶细胞。（iii）在转基因小鼠中，Ly-49（+）亚群获得了杀死C57 BL/6 ConA母细胞的能力，与C57 BL/6小鼠的Ly-49（+）NK细胞相反。其中通过对环境的选择或适应而施加的效应细胞上的低受体密度允许对潜在靶细胞上的还原的自身MHC配体的检测具有更高的灵敏度。
The Ly-49 molecule has been shown to interact with major histocompatibility complex (MHC) class I molecules, and the lytic function of Ly-49(+) natural killer (NK) cells from C57BL/(6) (H-2(b)) mice is inhibited by the recognition of H-2D(d) on tumor target cells, Introduction of a Ly-49 ligand, H-2D(d), into C57BL/6 mice did not alter the percentage of Ly-49(+) NK cells (13-18%), but it led to three functional effects on this subset. (i) The Ly-49 expression in the positive population was reduced by 30-50% compared to C57BL/6 control mice, (ii) While this Ly-49(+) subset (Ly-49lo) in the transgenic mice failed to kill BALB/c concanavalin A (Con A) blasts, which have high H-2D(d) expression, it was capable of killing SP2/O tumor cells, which have low H-2D(d) expression. Ly-49(+) NK cells (Ly-49hi) from nontransgenic mice failed to kill both of these H-2D(d)-expressing target cells, (iii) In the transgenic mice, the Ly-49(+) subset acquired the ability to kill C57BL/6 Con A blasts, in contrast to the Ly-49(+) NK cells of C57BL/6 mice, We propose a ''receptor-calibration'' hypothesis, where low receptor density on the effector cells imposed by selection or adaptation to the environment allows higher sensitivity for detection of reduced self-MHC ligands on potential target cells.