Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC, 27607, USA.
Bioinformatics Graduate Program, North Carolina State University, Raleigh, NC, 27695, USA.
Commun Biol. 2022 Dec 19;5(1):1387. doi: 10.1038/s42003-022-04344-2.
Rhesus cytomegalovirus (RhCMV)-based vaccination against Simian Immunodeficiency virus (SIV) elicits MHC-E-restricted CD8+ T cells that stringently control SIV infection in ~55% of vaccinated rhesus macaques (RM). However, it is unclear how accurately the RM model reflects HLA-E immunobiology in humans. Using long-read sequencing, we identified 16 Mamu-E isoforms and all Mamu-E splicing junctions were detected among HLA-E isoforms in humans. We also obtained the complete Mamu-E genomic sequences covering the full coding regions of 59 RM from a RhCMV/SIV vaccine study. The Mamu-E gene was duplicated in 32 (54%) of 59 RM. Among four groups of Mamu-E alleles: three ~5% divergent full-length allele groups (G1, G2, G2_LTR) and a fourth monomorphic group (G3) with a deletion encompassing the canonical Mamu-E exon 6, the presence of G2_LTR alleles was significantly (p = 0.02) associated with the lack of RhCMV/SIV vaccine protection. These genomic resources will facilitate additional MHC-E targeted translational research.
恒河猴巨细胞病毒（RhCMV）为基础的疫苗接种针对猴免疫缺陷病毒（SIV），引发了主要组织相容性复合体 E（MHC-E）限制的 CD8+T 细胞，严格控制约 55%接种恒河猴（RM）的 SIV 感染。然而，目前尚不清楚 RM 模型在多大程度上准确反映了人类 HLA-E 的免疫生物学。本研究通过长读测序，鉴定了 16 种 Mamu-E 同种型，并且在人类 HLA-E 同种型中检测到所有 Mamu-E 剪接连接。我们还从 RhCMV/SIV 疫苗研究中获得了涵盖 59 只 RM 全长编码区的完整 Mamu-E 基因组序列。Mamu-E 基因在 32 只（54%）RM 中发生了复制。在 4 组 Mamu-E 等位基因中：3 个约 5%不同的全长等位基因组（G1、G2、G2_LTR）和一个缺失包含经典 Mamu-E 外显子 6 的单态性组（G3），G2_LTR 等位基因的存在与 RhCMV/SIV 疫苗保护的缺乏显著相关（p=0.02）。这些基因组资源将促进针对 MHC-E 的进一步转化研究。
