S Oh, LP Perera, DS Burke, TA Waldmann, JA Berzofsky. (2004). " IL-15/IL-15Ralpha-mediated avidity maturation of memory CD8+ T cells. " Proc Natl Acad Sci U S A. 101, 15154-9. PMID: 15477598 DOI: 10.1073/pnas.0406649101
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.