An ELISPOT-Based Assay to Measure HBV-Specific CD8⁺ T Cell Responses in Immunocompetent Mice

Despite some important limitations, immunocompetent mouse models of HBV replication remain an essential tool for studying cellular and humoral immunity to the virus. CD8⁺ T cells are a critical component of the immune response to HBV due to their ability to both kill virus-infected hepatocytes and produce cytokines such as IFN-γ that non-cytopathically inhibit virus replication. A number of techniques can be used to measure the magnitude, specificity, and functionality of HBV-specific CD8⁺ T cells, each having its own unique advantages. We describe here the enzyme-linked immunospot (ELISPOT)-based assay, which, compared to other methods, is sensitive, cost-effective, and rapid and requires relatively little optimization, specialized training, or equipment.