Method to Study Adaptive NK Cells Following MCMV Infections

Immunological memory is a fundamental feature of the adaptive immune system that protects the host from recurrent infections from pathogens. Natural killer (NK) cells are a predominant member of the innate immune system that lack clonotypic receptors, which are essential for memory formation. However, evidence demonstrates that a unique subpopulation of NK cells develops adaptive-like features using germline-encoded receptors. Recent studies have shown that infection of cytomegalovirus (CMV) leads to clonal expansion of NKG2C⁺ and Ly49H⁺ NK cells, in humans and mouse, respectively. These activation receptors have the capability to recognize CMV-encoded proteins and facilitate a recall response upon reinfection. Although NK cells do not rearrange genes encoding their activating receptors as seen in B and T cells, they possess a selective process to generate memory features and a long-lived progeny. Here, we describe an established in vivo protocol for infecting mice with mouse cytomegalovirus (MCMV) to study an adaptive NK cell response.