Unconventional CD8⁺ T cell surveillance of cytomegalovirus via Qa-1/HLA-E-restricted epitope recognition.

ABSTRACT: Nonclassical CD8⁺ T cells can compensate for classical CD8⁺ T cell effector responses during murine cytomegalovirus (MCMV) infection. Through a combination of motif-based discovery, predictive algorithms, AlphaFold3 structural modeling, and biological assays, we identified multiple MCMV and human cytomegalovirus (HCMV) peptides that bind to Qa-1 and HLA-E, respectively. In the mouse system, we demonstrated that these virally encoded antigens stimulate Qa-1-restricted CD8⁺ T cells ex vivo, which can be tracked using MCMV peptide-loaded Qa-1 tetramers. Adoptive transfer of predominantly Qa-1 tetramer⁺ CD8⁺ T cells into RAG-1-deficient mice protects them from mortality, underscoring the critical role of these cells in host defense. Single

SUBMITTER: Reilly SP 

PROVIDER: S-EPMC12716397 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature