Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 364295
Title Identification of an interleukin-15 alpha receptor-binding site on human interleukin-15
Author(s) Bernard, J.; Harb, C.; Mortier, E.; Quemener, A.; Meloen, R.H.; Vermot-Desroches, C.; Wijdeness, J.; Dijken, J.P. van; Grotzinger, J.; Slootstra, J.W.; Plet, A.; Jacques, Y.
Source Journal of Biological Chemistry 279 (2004)23. - ISSN 0021-9258 - p. 24313 - 24322.
Department(s) ID - Dier en Omgeving
Publication type Refereed Article in a scientific journal
Publication year 2004
Keyword(s) cell growth-factor - alpha-chain - il-2 receptor - 3-dimensional structure - sequence alignment - il-15r-alpha chain - natural-killer - beta-chain - in-vivo - protein
Abstract 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.
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