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Characterization of an IL-2 mimetic with therapeutic potential.

Abstract : Human interleukin-2 (IL-2) interacts with two types of functional receptors (IL-2R alpha betagamma and IL-2R betagamma) and acts on a broad range of target cells involved in inflammatory reactions and immune responses. IL-2 is also used in different clinical trials aimed at improving the treatment of some cancers and the recovery of CD4 lymphocytes by HIV patients. The therapeutic index of IL-2 is limited by various side effects dominated by the vascular leak syndrome. We have shown that a chemically synthesised fragment of the IL-2 sequence can fold into a helical tetramer likely mimicking the quatemary structure of an hemopoietin. Indeed, peptide p1-30 (containing amino acids 1 to 30, including the sequence corresponding to the entire alpha helix A of IL-2) spontaneously folds into an alpha-helical homotetramer and stimulates the growth of T-cell lines expressing human IL-2R beta, whereas shorter versions of the peptide lack helical structure and are inactive. At the cellular level, p1-30 induces lymphokine-activated killer (LAK) cells and preferentially activates CD8 low lymphocytes and natural killer cells, which constitutively express IL-2R beta. A significant IFN-gamma production is also detected following p1-30 stimulation. A mutant form of p1-30 (Asp20-->Lys) which is likely unable to induce vascular leak syndrome remains capable to generate LAK cells like the original p1-30 peptide. Altogether our data suggest that p1-30 has therapeutic potential.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03144724
Contributor : Marie de Tarragon <>
Submitted on : Wednesday, February 17, 2021 - 6:47:30 PM
Last modification on : Thursday, March 25, 2021 - 3:20:06 AM

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  • HAL Id : pasteur-03144724, version 1
  • PUBMED : 11502078

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R Eckenberg, T Rose, J Moreau, R Weil, F Gesbert, et al.. Characterization of an IL-2 mimetic with therapeutic potential.. Cellular and Molecular Biology, R. Wegmann, 2001, 47 (4), pp.703-7. ⟨pasteur-03144724⟩

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