Martin, M. D. et al. Cell Rep. 31, 107508 (2020).

Recent studies report the failure of inbred mice to recapitulate the individuality of immune responses observed in genetically diverse populations. To map the diversity in the antiviral CD8+ T cell response, Martin et al. infected 47 mouse strains from the Collaborative Cross (CC) with acute lymphocytic choriomeningitis virus (LCMV) Armstrong. CC is an established recombinant mouse panel generated from diverse founder strains to better model human diseases. The researchers showed that, in comparison to inbred strains, CC strains produced varied quantities of cytokines during the innate immune response. This variation was indicative of the scale of the effector response and the size of the memory pool, suggesting that genetic factors underlying innate responses could inform T cell immunity. The authors confirmed these results using quantitative trait linking experiments. This study highlights the use of CC to discover genetic factors that may modulate antiviral responses, thus offering insight into T cell response diversity at a population level.