2022 journal article
Alternative splicing and genetic variation of mhc-e: implications for rhesus cytomegalovirus-based vaccines
COMMUNICATIONS BIOLOGY, 5(1).
AbstractRhesus 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 reflectsHLA-Eimmunobiology in humans. Using long-read sequencing, we identified 16Mamu-Eisoforms and allMamu-Esplicing junctions were detected amongHLA-Eisoforms in humans. We also obtained the completeMamu-Egenomic sequences covering the full coding regions of 59 RM from a RhCMV/SIV vaccine study. TheMamu-Egene was duplicated in 32 (54%) of 59 RM. Among four groups ofMamu-Ealleles: three ~5% divergent full-length allele groups (G1, G2, G2_LTR) and a fourth monomorphic group (G3) with a deletion encompassing the canonicalMamu-Eexon 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 additionalMHC-Etargeted translational research.