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非人类灵长类动物主要组织相容性复合体相关分子 1 序列变异体的特征。

Characterization of major histocompatibility complex-related molecule 1 sequence variants in non-human primates.

机构信息

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, 53711, USA.

Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53711, USA.

出版信息

Immunogenetics. 2019 Feb;71(2):109-121. doi: 10.1007/s00251-018-1091-1. Epub 2018 Oct 23.

Abstract

The major histocompatibility complex (MHC) class I-related molecule, MR1, presents vitamin B metabolites from bacteria and yeast to mucosal-associated invariant T (MAIT) cells. Despite the evolutionary conservation of MR1, we do not know whether different allele variants of MR1 exist within the nonhuman primate (NHP) populations that are commonly used for biomedical research. In this study, we identified 21 distinct MR1 nucleotide sequences representing 32 different alleles across five different NHP populations. The majority of the alleles conferring amino acid changes (allele variants) were found in or near the alpha-1 domain of the mature MR1 protein. We expressed four of the most commonly observed MR1 allele variants in 293T cells, and we found that each variant could present bacterial metabolites on the cell surface. We successfully induced cytokine production in macaque MAIT cells stimulated with 293T cells expressing the four most common MR1 allele variants, demonstrating the usefulness of these cell lines to study MAIT cell activity. Our data suggests that MR1 is not monomorphic, but that there are multiple MR1 alleles in NHPs. The materials we describe here will be valuable for characterizing differences in MR1 antigen presentation and MAIT cell function in NHPs.

摘要

主要组织相容性复合体 (MHC) Ⅰ类相关分子 MR1 将细菌和酵母的维生素 B 代谢物呈递给黏膜相关不变 T (MAIT) 细胞。尽管 MR1 在进化上是保守的,但我们不知道在常用于生物医学研究的非人类灵长类动物 (NHP) 群体中是否存在不同的 MR1 等位基因变异体。在这项研究中,我们在五个不同的 NHP 群体中鉴定了 21 个不同的 MR1 核苷酸序列,代表 32 个不同的等位基因。赋予氨基酸变化的大多数等位基因(等位基因变异体)位于成熟 MR1 蛋白的 alpha-1 结构域内或附近。我们在 293T 细胞中表达了四种最常见的 MR1 等位基因变异体,发现每种变异体都可以在细胞表面呈现细菌代谢物。我们成功地诱导了用表达四种最常见 MR1 等位基因变异体的 293T 细胞刺激的猕猴 MAIT 细胞产生细胞因子,证明了这些细胞系在研究 MAIT 细胞活性方面的有用性。我们的数据表明,MR1 不是单态的,而是在 NHP 中有多个 MR1 等位基因。我们在这里描述的材料将有助于表征 NHP 中 MR1 抗原呈递和 MAIT 细胞功能的差异。

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