Viral MHC class I inhibition evades CD8⁺ T-cell effector responses in vivo but not CD8⁺ T-cell priming

Although viral MHC class I inhibition is considered a classic immune-evasion strategy, its in vivo role is largely unclear. Mutant cowpox virus lacking its MHC class I inhibitors is markedly attenuated during acute infection because of CD8⁺ T-cell-dependent control, but it was not known how CD8⁺ T-cell responses are affected. Interestingly, we found no major effect of MHC class I downregulation on priming of functional cowpox virus-specific CD8⁺T cells. Instead, we demonstrate that, during acute infection in vivo, MHC class I down-regulation prevents primed virus-specific CD8⁺ T cells from recognizing infected cells and exerting effector responses to control the infection.