title: Altered immunodominance hierarchies of influenza A virus-specific H-2(b)-restricted CD8+ T cells in the absence of terminal deoxynucleotidyl transferase.
abstract: Immunodominance is considered an obstacle to successful T cell-based vaccination, and constant efforts are made to uncover the underlying mechanisms for this phenomenon. We have examined the contribution of terminal deoxynucleotidyl transferase (TdT), whose function accounts for approximately 90% of T cell receptor diversity, to dominance hierarchies of H-2(b)-restricted flu-specific T(CD8+). Using intracellular cytokine staining to quantitatively detect epitope-specific T(CD8+), we demonstrate that TdT-deficient mice exhibit a distinct hierarchical pattern in their primary and recall T(CD8+) responses to influenza A viruses, which results from skewed responsiveness towards select influenza epitopes. Our data establish a link between TdT and immunodominance in H-2(b)-restricted antiviral T(CD8+) responses.
authors.affiliation: Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Matilde
authors.initials: M
authors.lastname: Leon-Ponte
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kasprzyski
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Mannik
authors.forename: S M Mansour
authors.initials: SM
authors.lastname: Haeryfar
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004253:DNA Nucleotidylexotransferase / Q000172:deficiency / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D016056:Immunodominant Epitopes; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D016056:Immunodominant Epitopes; D004253:DNA Nucleotidylexotransferase