Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 42, Pages 15154-15159Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0406649101
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T cell avidity is critical to viral clearance, but mechanisms of CD8(+) T cell avidity maturation are poorly understood. Here, we find that IL-15 mediates two mechanisms of avidity maturation. (i) By selection at the population level, IL-15 promotes greater survival of high- compared with low-avidity cytotoxic T lymphocytes (CTLs). High-avidity CTLs express higher levels of IL-15Ralpha and persist longer by homeostatic proliferation. (ii) At the individual cell level, IL-15 induces higher levels of surface coreceptor CD8alphabeta, increasing functional avidity. IL-15 during priming selects or induces higher-avidity CTLs. Conversely, high-avidity CTLs are diminished in IL15Ralpha knockout mice. These results provide an explanation of CD8+ T cell avidity maturation and may contribute to the design of novel vaccines.
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