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

Sang Kon Oh, Liyanage P. Perera, Donald S. Burke, Thomas A. Waldmann, Jay A. Berzofsky

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)15154-15159
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number42
DOIs
StatePublished - Oct 19 2004

ASJC Scopus subject areas

  • General

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