title: CD8+ T cell immunodominance in lymphocytic choriomeningitis virus infection is modified in the presence of toll-like receptor agonists.
abstract: Currently, we have limited understanding of how Toll-like receptor (TLR) engagement by microbial products influences the immune response during a concurrent virus infection. In this study, we established that dual TLR2 plus TLR3 (designated TLR2+3) stimulation alters the immunodominance hierarchies of lymphocytic choriomeningitis virus (LCMV) epitopes by reducing NP396-specific CD8+ T cell responses and shifting it to a subdominant position. The shift in immunodominance occurred due to a reduction in antigen uptake and the reduced cross-presentation of NP396, a major LCMV immunodominant epitope that is efficiently cross-presented. Moreover, the altered immunodominance was dependent on TLR stimulation occurring at the site of infection. Finally, as lipopolysaccharide failed to induce the same phenomenon, the data suggest that these findings are dependent not only on the dual engagement of the TRIF/MyD88 pathways but also on how TLR agonists activate antigen-presenting cells. Taken together, our data demonstrate a novel role for TLR ligands in regulating antiviral CD8+ T cell responses due to the regulation of the cross-presentation of cell-associated antigens.
authors.affiliation: Department of Microbiology and Immunology, Queen's University, Botterell Hall, Room 739, Kingston, Ontario, K7L 3N6, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Sameh
authors.initials: S
authors.lastname: Basta
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007155:Immunologic Factors / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D007155:Immunologic Factors; D051193:Toll-Like Receptors