Altered immunodominance hierarchies of influenza A virus-specific H-2(b)-restricted CD8+ T cells in the absence of terminal deoxynucleotidyl transferase.
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.
Leon-Ponte
Matilde
M
Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada.
Kasprzyski
Tomasz
T
Mannik
Lisa A
LA
Haeryfar
S M Mansour
SM
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
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D016056:Immunodominant Epitopes; D004253:DNA Nucleotidylexotransferase