Evidence that HLA-G is the functional homolog of mouse Qa-2, the Ped gene product
Evidence that HLA-G is the functional homolog of mouse Qa-2, the Ped gene product
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DOI：
10.1016/j.humimm.2003.08.352
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发表时间：
2003-11-01
期刊：
影响因子：
2.7
通讯作者：
Warner, CM
中科院分区：
文献类型：
--
作者：
Comiskey, M;Goldstein, CY;Warner, CM
Qa-2是一种常规的b类主要组织相容性复合体（MHC）分子，可能是人白细胞抗原G （HLA-G）的功能同源物。这两种分子都与免疫调节和胚胎发育有关，并且都存在于通过选择性剪接产生的膜结合和可溶性同种异构体中。可溶性剪接变异体与HLA-G的生殖功能有关。虽然以前在T淋巴细胞中检测到Qa-2的可溶性变体，但我们现在证明了在8细胞胚胎和囊胚中存在两种已知的Qa-2可溶性形式之一的mRNA。Qa-2是连接在细胞膜外小叶的糖基磷脂酰肌醇（GPI），存在于脂筏微域中，其他筏相关蛋白将信号转导到细胞中。相反，HLA-G具有截断的6个氨基酸的细胞质尾部。通过荧光共定位在JEG-3细胞中，利用荧光霍乱毒素β亚基（一种脂筏标记）和抗HLA-G抗体，我们证明了膜结合的HLA-G也定位于脂筏，这与两个分子之间的功能同源性一致。最后，我们的实验中，我们纯化了Qa-2，并通过一种称为蛋白质绘画的过程将其转移到Qa-2阴性细胞中，这代表了一种涉及HLA-G的潜在治疗模型。人类免疫学64,999-1004（2003）。(C)美国组织相容性与免疫遗传学学会，2003。Elsevier Inc.出版。
Qa-2, a routine class Ib major histocompatibility complex (MHC) molecule, is a possible functional homolog of human leukocyte antigen G (HLA-G). Both molecules have been implicated in immunoregulation and embryonic development and both occur in membrane-bound and soluble isoforms that arise by alternative splicing. Soluble splice variants have been implicated in the reproductive functions of HLA-G. While soluble variants of Qa-2 have been previously detected in T lymphocytes, we now demonstrate the presence of mRNA for one of the two known soluble forms of Qa-2 in eight-cell embryos and in blastocysts. Qa-2 is glycosylphosphatidylinositol (GPI) linked in the outer leaflet of the cell membrane and is found in lipid raft microdomains where other raft-associated proteins transduce signals into the cell. In contrast, HLA-G has a truncated six amino acid cytoplasmic tail. By fluorescence co-localization in JEG-3 cells, using fluorescent cholera toxin beta subunit (a lipid raft marker) and anti-HLA-G antibody, we have demonstrated that membrane-bound HLA-G also localizes to lipid rafts, consistent with functional homology between the two molecules. Finally, our experiments in which we have purified Qa-2 and transferred it via a process known as protein painting to Qa-2 negative cells represent a model for potential therapy involving HLA-G. Human Immunology 64, 999-1004 (2003). (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Inc.