The murine MHC class I genes, H-2Dq and H-2Lq, are strikingly homologous to each other, H-2Ld, and two genes reported to encode tumor-specific antigens.
The murine MHC class I genes, H-2Dq and H-2Lq, are strikingly homologous to each other, H-2Ld, and two genes reported to encode tumor-specific antigens.
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DOI：
10.1084/jem.168.5.1719
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发表时间：
1988-11-01
期刊：
影响因子：
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通讯作者：
Hansen TH
中科院分区：
文献类型：
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作者：
Lee DR;Rubocki RJ;Lie WR;Hansen TH
似乎有两种现象可区分D区I类基因与鼠MHC K区中的D区I类基因：（a）已观察到表达的D区I类分子数量的单倍型差异;和（B）在不同H-2单倍型的小鼠之间和小鼠内，可确定密切相关的D区I类分子的谱系。这两个观察结果都是基于这些分子的血清学和肽图谱分析。最近使用分子生物学方法的报告证实了这些发现。由于小鼠品系B10.AKM表达多种D区I类抗原，所有这些抗原都与原型Ld分子密切相关，因此我们使用分子方法研究了B10.AKM的Dq区。从基因组B10.AKM噬菌体和粘粒文库中分离到3个D区I类基因。基于这些基因与BALB/c的D区I类基因的类似的限制性内切酶位点，并通过这些基因与D4 d基因衍生的寡核苷酸探针杂交的比对，我们已经指定这些基因为Dq，Lq和D4 q。如通过DNA介导的基因转移至小鼠L细胞，随后通过血清学分析所确定的，Dq和Lq基因编码先前表征的Dq区域I类抗原。Dq和Lq基因的核酸序列比较表明与Ld和Db基因的同源性高于与其他D区I类基因的同源性。此外，用Dq、Lq或Ld基因转染子刺激的CTL与作为靶的其他转染子显示出强烈的交叉反应，表明这些基因的产物在功能上也相关。因此，这些研究表明，L分子代表了几个D区基因产物共享的原型结构，此外，Ld样祖基因的复制导致了两个Dq区I类基因，Dq和Lq。出乎意料的是，确定的Dq和Lq基因的序列几乎相同的两个基因，A166和A149，分别被报道编码肿瘤特异性抗原的序列;这些新的I类基因分离自H-2k纤维肉瘤，1591。这就提出了一种明显的可能性，即这些所谓的肿瘤特异性I类基因是通过污染引入该肿瘤的。
Two phenomena appear to distinguish the D region class I genes from those in the K region in the murine MHC: (a) haplotype disparity in the number of expressed D region class I molecules has been observed; and (b) clines of closely related D region class I molecules among and within mice of different H-2 haplotypes can be defined. Both of these observations have been based on serological and peptide mapping analyses of these molecules. Recent reports using molecular biological approaches have corroborated these findings. Since the mouse strain B10.AKM expresses multiple D region class I antigens, all of which are closely related to the prototypic Ld molecule, we investigated the Dq region of B10.AKM using molecular approaches. Three D region class I genes were isolated from genomic B10.AKM bacteriophage and cosmid libraries. Based on alignment of those genes with the BALB/c D region class I genes by analogous restriction endonuclease sites and by hybridization of one of those genes with a D4d gene-derived oligonucleotide probe, we have designated these genes as Dq, Lq, and D4q. As determined by DNA-mediated gene transfer to mouse L cells followed by serological analyses, the Dq and Lq genes encode previously characterized Dq region class I antigens. The nucleic acid sequence comparisons of the Dq and Lq genes demonstrated a higher level of homology with the Ld and Db genes than with other D region class I genes. In addition, CTL stimulated with a Dq, Lq, or Ld gene transfectant showed strong crossreactions with the other transfectants as targets, suggesting that the products of these genes are also functionally related. Thus, these studies suggest that the L molecule represents a prototypic structure shared by several D region gene products, and furthermore, the duplication of an Ld-like progenitor gene resulted in two Dq region class I genes, Dq and Lq. Unexpectedly, the sequences determined for the Dq and Lq genes are nearly identical to the sequences of two genes, A166 and A149, respectively, which were reported to encode the tumor-specific antigens; these novel class I genes were isolated from an H-2k fibrosarcoma, 1591. This raises the distinct possibility that these purported tumor-specific class I genes were introduced into this tumor by contamination.