Class II multiformity generated by variable MHC-DRB region configurations in the California sea lion (Zalophus californianus)

Class II multiformity generated by variable MHC-DRB region configurations in the California sea lion (Zalophus californianus)
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DOI:
10.1007/s00251-004-0655-4
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发表时间:
2004-04-01
期刊:
影响因子:
3.2
通讯作者:
Johnson, ML
Johnson, ML
中科院分区:
医学4区
文献类型:
--
作者:
Bowen, L;Aldridge, BM;Johnson, ML

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鉴于主要组织相容性复合体 (MHC) 中编码的分子的免疫学重要性,有大量研究检查这些基因在野生动物种群中的变异性。许多这些研究的基本假设是,MHC 多样性总是源自单个基因位点的高水平等位基因变异,从而导致对 MHC 多态性明显有限的繁荣物种的广泛描述。事实上,在之前的一项研究中,我们未能在加州海狮的 MHC II 类(DQA 和 DQB)基因中找到与传统上多样化的肽结合功能兼容的序列特征,因此将多态性的搜索范围扩大到了 DRA 和 DRB 基因。我们的结果表明,与 Zaca-DQA、-DQB 和 -DRA 相比,Zaca-DRB 具有与抗原结合和呈递兼容的序列特征。事实上,Zac-DRB 构成了一个基因家族,包含至少七个基因座,每个基因座都表现出有限的变异性,并且在个体之间以可变的配置存在。这种产生 MHC DRB 多样性的不寻常机制与在恒河猴中观察到的机制相似,但尚未在任何其他物种中报道过。在加州海狮中鉴定出一种新的 II 类 MHC 变异系统,证明了对其他海洋物种免疫遗传多样性的组织基础及其在传染病易感性中的作用的新研究的合理性。
In light of the immunological importance of molecules encoded within the major histocompatibility complex (MHC), there are numerous studies examining the variability of these genes in wildlife populations. An underlying assumption in many of these studies is that MHC diversity invariably arises from a high level of allelic variation at a single gene locus, leading to widespread descriptions of thriving species with apparently limited MHC polymorphism. Indeed, in a previous study we failed to find sequence features compatible with traditionally diverse peptide-binding functions in MHC class II (DQA and DQB) genes in California sea lions and therefore expanded the search for polymorphism to the DRA and DRB genes. Our results show that, in contrast to Zaca-DQA, -DQB, and -DRA, Zaca-DRB has sequence features compatible with antigen binding and presentation. In fact Zaca-DRB constitutes a gene family, comprising at least seven loci, each of which exhibits limited variability, and which are present in variable configurations between individuals. This unusual mechanism for generating MHC DRB diversity is similar to that observed in the rhesus macaque, but has not been reported in any other species. The identification of a novel system of class II MHC variability in the California sea lion justifies new studies into the organizational basis of immunogenetic diversity in other marine species, and its role in infectious disease susceptibility.