Alternative splicing and genetic variation of mhc-e: implications for rhesus cytomegalovirus-based vaccines

Hayden Brochu, Ruihan Wang, Tammy Tollison, Chul Woo Pyo, Alexander Thomas, Elizabeth Tseng, Lynn Law, Louis J. Picker, Michael Gale, Daniel E. Geraghty, Xinxia Peng

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1387
JournalCommunications Biology
Volume5
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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