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Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15154-9. Epub 2004 Oct 11.

IL-15/IL-15Ralpha-mediated avidity maturation of memory CD8+ T cells.

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  • 1Vaccine Branch and Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.


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 IL-15Ralpha 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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