Cross-Priming of a Single Viral Protein from Lymphocytic Choriomeningitis Virus Alters Immunodominance Hierarchies of CD8 + T Cells during Subsequent Viral Infections

Immunogenic epitopes that stimulate CD8⁺ T cells can be organized into an immunodominance hierarchy, based on their ability to induce T-cell priming and subsequent expansion. Cytotoxic CD8⁺ T cells can be primed through the cross-priming pathway, where exogenous viral proteins are acquired by professional antigen-presenting cells (pAPCs). We have previously reported that lymphocytic choriomeningitis nucleoprotein (LCMV-NP) expressed in HEK cells (HEK-NP) induces cross-priming of CD8⁺ T cells in vivo. In this study, we have used this HEK-NP model to study the effects of LCMV-NP cross-priming on the LCMV immunodominance hierarchy following viral challenge. Our results highlight the contribution of cross-priming to the immune response, since the T-cell hierarchy was significantly altered as a result of exogenous processing of a single virus protein, and this phenomenon was maintained throughout the memory response. Moreover, as a result of cross-priming, in vivo CD8⁺ T-cell killer activity was enhanced during subsequent virus assaults. These findings have significant implications for immunotherapy because they demonstrate that exogenous delivery of specific T-cell epitopes can be utilized to manipulate the host's CD8⁺ T-cell memory immunodominance responses.