The ability of H-2Dd molecule to affect natural resistance to hemopoietic allografts is an intrinsic property shared by Ddm1 but not Ld.
The ability of H-2Dd molecule to affect natural resistance to hemopoietic allografts is an intrinsic property shared by Ddm1 but not Ld.
复制标题
H-2Dd 分子影响造血同种异体移植天然抗性的能力是 Ddm1 所共有的固有特性，但 Ld 没有。
DOI：
10.1002/eji.1830240210
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发表时间：
1994
影响因子：
5.4
通讯作者：
Nakamura,I
中科院分区：
文献类型：
--
作者：
Milisauskas,VK;Nakamura,I
F1杂种对亲本骨髓移植物的抗性（HR）由自然杀伤（NK）细胞介导，并被认为是由与主要组织相容性复合体（MHC）相关的非I类造血组织相容性（Hh）基因控制。然而，在体外NK细胞对造血靶细胞的细胞毒性中，某些I类MHC分子的表达确实影响HR，尽管这种作用的机制尚不清楚。在这项研究中，我们研究了I类分子的“自我/非自我”性质和负责此功能的分子结构域的相关性。用1类H-2Ddor Ld基因转染H-2b/Hh-1淋巴瘤细胞，通过检测转染子竞争性抑制亲本H-2b/Hh-1b骨髓移植物被辐照的F1杂交宿主体内排斥反应的能力来检查其对Hh-1表型的影响。转染子的多个独立克隆显示，Dd基因的基因组或cDNA，而不是Ld的基因组或cDNA，使Hh-1b-阳性细胞不能抑制F1小鼠中的HR，尽管这两个基因属于相同单倍型的相同区域。不仅在Dd和Ldare自身的H-2b/dF 1小鼠中可以观察到相同的效果，而且在Dd和Ldare非自身的H-2b/kF 1小鼠中也可以观察到相同的效果。因此，Dd分子的这种功能是一种内在特性，不一定与其相对于效应细胞的自身/非自身特性相关。此外，考虑到本研究中使用的测定的性质，结果支持“靶标干扰”模型作为Ddeffect的潜在机制。为了定位Dd分子的相关结构域，检测了突变型Ddm 1基因，发现其与非突变型Dd具有相同的作用。Ddm 1是Dd和Ld之间的杂合分子，与Dd仅共享α1结构域和部分α2结构域。Ddm 1的两个N末端结构域与Dd的N末端结构域有三个氨基酸取代，其中两个影响分子的肽结合特性。
F1hybrid resistance (HR) to parental bone marrow grafts is mediated by natural killer (NK) cells, and thought to be controlled by the non‐class I hemopoietic histocompatibility (Hh) genes linked to the major histocompatibility complex (MHC). However, as in thein vitroNK cytotoxicity against hemopoietic targets, expression of certain class I MHC molecules does affect HR, although mechanisms underlying such an effect are not understood. In this study, we examine the relevance of the “self/non‐self” property of class I molecules and the molecular domains responsible for this function. H‐2b/Hh‐1blymphoma cells were transfected with class 1 H‐2Ddor Ldgene, and its effect on the Hh‐1 phenotype was examined by testing the transfectant's ability to competitively inhibit thein vivorejection of parental H‐2b/Hh‐1bbone marrow grafts by irradiated F1hybrid hosts. Multiple independent clones of transfectants show that the genomic or cDNA of the Ddgene, but not of Ld, renders the Hh‐1b‐positive cells incapable of inhibiting HR in F1mice, although both genes belong to the same region of the same haplotype. The same effect could be observed not only in H‐2b/dF1mice for which Ddand Ldare self, but also in H‐2b/kF1mice for which both Ddand Ldare non‐self. Thus, this function of the Ddmolecule is an intrinsic property, not necessarily related to its self/non‐self characteristic relative to the effector cells. Furthermore, given the nature of the assay used in this study, the results favor a “target interference” model as the underlying mechanism of the Ddeffect. To locate the relevant domain(s) of the Ddmolecule, mutant Ddm1gene was tested and found to have the same effect as the non‐mutant Dd. Ddm1is a hybrid molecule between Ddand Ld, sharing with Ddonly the α1 domain and a portion of the α2 domain. The two N‐terminal domains of Ddm1differ from those of Ddby three amino acid substitutions, two of which affect the molecules' peptide‐binding properties.