NDLI: The influenza virus-specific CTL immunodominance hierarchy in mice is determined by the relative frequency of high-avidity T cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chadderton, Jesseka La Gruta, Nicole L. Cukalac, Tania Kan, Wan Ting Jackson, David C. Zeng, Weiguang Cullen, Jolie G. Doherty, Peter C. Turner, Stephen J.
Description	Country affiliation: Australia Author Affiliation: Cukalac T ( Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.)
Abstract	Virus-specific CTL responses typically fall into reproducible hierarchies with particular epitopes eliciting either immunodominant or subdominant responses after viral challenge. The recently acquired capacity to directly enumerate naive CTL precursors (CTLps) in both mice and humans has implicated CTLp frequency as a key predictor of immune response magnitude after Ag challenge. However, recent studies have indicated that naive CTLp frequencies do not necessarily predict the size of the Ag-driven response, indicating an important role for differential CTLp recruitment and/or expansion. This study characterizes the early emergence of various influenza epitope-specific CTL responses at multiple sites in C57BL/6 mice, and probes the role of Ag dose and TCR avidity in dictating immune response hierarchies. Despite large naive CTLp numbers, subdominance was found to arise largely as a consequence of the abrupt and premature cessation of CTL proliferation, at least for one epitope specificity. Investigation into the possible drivers of the poor proliferation observed for subdominant specificities showed that the immunodominance hierarchy endured irrespective of epitope abundance, and correlated with the prevalence of high-avidity T cells in both the naive and immune compartments. Our study strongly indicates that the quality, and not simply the quantity, of antiviral CTLs dictate response magnitude.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	9
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Immunodominant Epitopes Immunology Influenza A Virus Lymphocyte Activation T-lymphocytes, Cytotoxic Animals Cell Separation Cytotoxicity, Immunologic Flow Cytometry Mice Mice, Inbred C57bl Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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