Research ArticleHIV

Cytomegaloviral determinants of CD8+ T cell programming and RhCMV/SIV vaccine efficacy

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Science Immunology  25 Mar 2021:
Vol. 6, Issue 57, eabg5413
DOI: 10.1126/sciimmunol.abg5413

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Unconventional responses

The 68-1 rhesus cytomegalovirus (RhCMV) vectors that express simian immunodeficiency virus (SIV) inserts induce major histocompatibility complex E (MHC-E)– and MHC-II–restricted, SIV-specific CD8+ T cell responses, but the mechanisms responsible for this unconventional MHC restriction and its contribution to RhCMV/SIV vaccine efficacy are poorly understood. Malouli et al. show that these responses result from genetic rearrangements in 68-1 RhCMV that disrupt the function of eight immunomodulatory proteins encoded by the Rh157.5/Rh157.4 and Rh158-161 genomic regions. Repair of each of these genes with either RhCMV or human CMV counterparts shifted responses to an MHC-Ia–restricted or a mixture of MHC-Ia– and MHC-II–restricted CD8 T cell responses but did not protect against SIV. These data suggest that MHC-E–restricted CD8+ T cell responses are critical to protection against SIV.

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