Identification of an interleukin-15 alpha receptor-binding site on human interleukin-15

J. Bernard, C. Harb, E. Mortier, A. Quemener, R.H. Meloen, C. Vermot-Desroches, J. Wijdeness, J.P. van Dijken, J. Grotzinger, J.W. Slootstra, A. Plet, Y. Jacques

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    55 Citations (Scopus)


    To identify the epitopes in human Interleukin-15 (IL-15) that are responsible for binding to the interleukin-15 receptor -chain, antibody as well as receptor mapping by peptide scanning and site-directed mutagenesis was used. By peptide scanning, we identified four regions in IL-15: the first one (85CKECEELEEKN95) is located in the C-D loop and is recognized by a set of non-inhibitory antibodies. The second region (102SFVHIVQMFIN112) is located in helix D and is recognized by two antibodies that are inhibitory of IL-15 bio-activity, but not of IL-15 binding to IL-15R. The two remaining regions react with a recombinant soluble form of the IL-15R: the first (44LLELQVISL52, peptide 1) corresponds to a sequence located in the B helix and the second (64ENLII68, peptide 2) to a sequence located in helix C. The latter is also contained in the epitope recognized by an antibody (mAb B-E29) that prevents IL-15 binding to IL-15R. By site directed mutagenesis, we confirmed that residues present in peptide 1 (L45, E46, V49, S51, L52) and peptide 2 (L66 and I67) are involved in the binding of IL-15 to IL-15R. Furthermore, the results presented indicate that residues in the second peptide (E64, N65, I68) participate in IL-2R recruitment. This finding could have implications on the dynamic of receptor assembly. These results also indicate that the modes of interaction of IL-15 and IL-2 with their respective {alpha) chains are not completely analogous. Finally, some of the IL-15 mutants generated in this study displayed agonist or antagonist properties and may be useful as therapeutic agents.
    Original languageEnglish
    Pages (from-to)24313-24322
    JournalJournal of Biological Chemistry
    Issue number23
    Publication statusPublished - 2004


    • cell growth-factor
    • alpha-chain
    • il-2 receptor
    • 3-dimensional structure
    • sequence alignment
    • il-15r-alpha chain
    • natural-killer
    • beta-chain
    • in-vivo
    • protein


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