NLRC5 deficiency has a moderate impact on immunodominant CD8 + T cell responses during rotavirus infection of adult mice.

The NOD-like receptor (NLR) family plays an important role in innate immunity. CIITA and NLRC5 are unusual members of the NLR family that instead of recognizing pathogen-associated or damage-associated molecular patterns, form enhanceosomes with adaptor molecules and modulate major histocompatibility complex (MHC) class II and MHC class I expression, respectively. While NLRC5 has been shown to play a role during intracellular pathogen infection and tumor cell immune evasion, its role in regulating antigen-specific CD8+ T cell responses at the intestinal mucosa has not been investigated. Here, we take advantage of the rotavirus model in adult mice to dissect the impact of NLRC5 on CD8+ T cell responses to this viral infection at the gut mucosa. We show that while Nlrc5-/- mice exhibited normal proportions of T cell sub-populations in the intraepithelial and lamina propria compartments, these mice had decreased baseline MHC class I expression on various immune cells in the lamina propria. Upon rotavirus infection, Nlrc5 deficiency resulted in impaired H2-Kb -restricted antigen-specific CD8+ T cell responses, which was recapitulated in mice deficient for Nlrc5 within the dendritic cell compartment. The impaired CD8+ T cell response in Nlrc5-/- mice was not significant enough to impact viral titres, suggesting compensation in Nlrc5-/- mice, perhaps as a result of higher numbers of activated B cells in the mesenteric lymph nodes and normal rotavirus-specific immunoglobulin A responses. Collectively, our results demonstrate a minor role for NLRC5 in modulating H2-Kb -restricted antigen-specific CD8+ T cell responses in the small intestine during rotavirus infection in adult mice. This article is protected by copyright. All rights reserved.