Oh, SK and Perera, LP and Burke, DS and Waldmann, TA and Berzofsky, JA
(2004)
IL-15/IL-15Rα-mediated avidity maturation of memory CD8<sup>+</sup> T cells.
Proceedings of the National Academy of Sciences of the United States of America, 101 (42).
15154 - 15159.
ISSN 0027-8424
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Abstract
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-15Rα and persist longer by homeostatic proliferation. (ii) At the individual cell level, IL-15 induces higher levels of surface coreceptor CD8αβ, increasing functional avidity. IL-15 during priming selects or induces higher-avidity CTLs. Conversely, high-avidity CTLs are diminished in IL-15Rα 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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