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.
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D045142:Cross-Priming / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D009698:Nucleoproteins; D014764:Viral Proteins