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Human cytomegalovirus UL18 prevents priming of MHC-E- and MHC-II-restricted CD8 + T cells.

Authors :
Malouli D
Taher H
Mansouri M
Iyer RF
Reed J
Papen C
Schell JB
Beechwood T
Martinson T
Morrow D
Hughes CM
Gilbride RM
Randall K
Ford JC
Belica K
Ojha S
Sacha JB
Bimber BN
Hansen SG
Picker LJ
Früh K
Source :
Science immunology [Sci Immunol] 2024 Oct 11; Vol. 9 (100), pp. eadp5216. Date of Electronic Publication: 2024 Oct 11.
Publication Year :
2024

Abstract

Rhesus cytomegalovirus (RhCMV) vectors elicit major histocompatibility complex (MHC)-E-restricted CD8 <superscript>+</superscript> T cells that stringently control simian immunodeficiency virus (SIV) in rhesus macaques. These responses require deletion of eight RhCMV chemokine-like open reading frames (ORFs) that are conserved in human cytomegalovirus (HCMV). To determine whether HCMV encodes additional, nonconserved inhibitors of unconventional T cell priming, we inserted 41 HCMV-specific ORFs into a chemokine-deficient strain (68-1 RhCMV). Monitoring of epitope recognition revealed that HCMV UL18 prevented unconventional T cell priming, resulting in MHC-Ia-targeted responses. UL18 is homologous to MHC-I but does not engage T cell receptors and, instead, binds with high affinity to inhibitory leukocyte immunoglobulin-like receptor-1 (LIR-1). UL18 lacking LIR-1 binding no longer interfered with MHC-E-restricted T cell stimulation by RhCMV-infected cells or the induction of unconventionally restricted T cells. Thus, LIR-1 binding needs to be deleted from UL18 of HCMV/HIV vaccines to allow for the induction of protective MHC-E-restricted T cells.

Details

Language :
English
ISSN :
2470-9468
Volume :
9
Issue :
100
Database :
MEDLINE
Journal :
Science immunology
Publication Type :
Academic Journal
Accession number :
39392895
Full Text :
https://doi.org/10.1126/sciimmunol.adp5216