Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33766941.
- Also identified by DOI 10.1126/science.abe9233 and PMC identifier 8354429.
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Abstract
Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8<sup>+</sup> T cells recognizing epitopes presented by major histocompatibility complex II (MHC-II) and MHC-E but not MHC-Ia. These immune responses mediate replication arrest of SIV in 50 to 60% of monkeys. We show that the peptide VMAPRTLLL (VL9) embedded within the RhCMV protein Rh67 promotes intracellular MHC-E transport and recognition of RhCMV-infected fibroblasts by MHC-E-restricted CD8<sup>+</sup> T cells. Deletion or mutation of viral VL9 abrogated MHC-E-restricted CD8<sup>+</sup> T cell priming, resulting in CD8<sup>+</sup> T cell responses exclusively targeting MHC-II-restricted epitopes. These responses were comparable in magnitude and differentiation to responses elicited by 68-1 vectors but did not protect against SIV. Thus, Rh67-enabled direct priming of MHC-E-restricted T cells is crucial for RhCMV/SIV vaccine efficacy.
Medical subject headings
- CD8-Positive T-Lymphocytes
- Cytomegalovirus
- Genetic Vectors
- Histocompatibility Antigens Class I
- Peptide Fragments
- SAIDS Vaccines