@article{a8c1136fc63b4bf9b92c2a910cd6463d,
title = "Alternative splicing and genetic variation of mhc-e: implications for rhesus cytomegalovirus-based vaccines",
abstract = "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.",
author = "Hayden Brochu and Ruihan Wang and Tammy Tollison and Pyo, {Chul Woo} and Alexander Thomas and Elizabeth Tseng and Lynn Law and Picker, {Louis J.} and Michael Gale and Geraghty, {Daniel E.} and Xinxia Peng",
note = "Funding Information: This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201800008C and Contract No. HHSN272201600027C. Funding for this study was supported in part by the National Institutes of Health, Office of the Director P51OD010425. Research reported in this publication was supported by the University of Washington / Fred Hutch Center for AIDS Research, an NIH-funded program under award number AI027757 which is supported by the following NIH Institutes and Centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, and NIDDK. This work was supported by National Institute of Allergy and Infectious Diseases (NIAID) grants P01 AI094417, U19 AI128741, and UM1 AI124377 (to L.J.P.) and an Oregon National Primate Research Center Core grant from the National Institutes of Health, Office of the Director (P51 OD011092). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s42003-022-04344-2",
language = "English (US)",
volume = "5",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}