生物
假基因
人类白细胞抗原
效应器
免疫系统
细胞生物学
基因
分子生物学
遗传学
作者
Lucas Hubert,Julien Paganini,Christophe Picard,Jacques Chiaroni,Laurent Abi-Rached,Pierre Pontarotti,Julie Di Cristofaro
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2021-12-06
卷期号:: ji2100358-ji2100358
标识
DOI:10.4049/jimmunol.2100358
摘要
The biological relevance of genes initially categorized as “pseudogenes” is slowly emerging, notably in innate immunity. In the HLA region on chromosome 6, HLA-H is one such pseudogene; yet, it is transcribed, and its variation is associated with immune properties. Furthermore, two HLA-H alleles, H*02:07 and H*02:14, putatively encode a complete, membrane-bound HLA protein. Here we thus hypothesized that HLA-H contributes to immune homeostasis similarly to tolerogenic molecules HLA-G, -E, and -F. We tested if HLA-H*02:07 encodes a membrane-bound protein that can inhibit the cytotoxicity of effector cells. We used an HLA-null human erythroblast cell line transduced with HLA-H*02:07 cDNA to demonstrate that HLA-H*02:07 encodes a membrane-bound protein. Additionally, using a cytotoxicity assay, our results support that K562 HLA-H*02:07 inhibits human effector IL-2–activated PBMCs and human IL-2–independent NK92-MI cell line activity. Finally, through in silico genotyping of the Denisovan genome and haplotypic association with Denisovan-derived HLA-A*11, we also show that H*02:07 is of archaic origin. Hence, admixture with archaic humans brought a functional HLA-H allele into modern European and Asian populations.
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