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Titolo:
Characterization of an IL-2 mimetic with therapeutic potential
Autore:
Eckenberg, R; Rose, T; Moreau, JL; Weil, R; Gesbert, F; Dubois, S; Tello, D; Bossus, M; Gras, H; Tartar, A; Bertoglio, J; Chouaib, S; Jacques, Y; Alzari, PM; Theze, J;
Indirizzi:
Inst Pasteur, Dept Immunol, Unite Immunogenet, F-75724 Paris 15, France Inst Pasteur Paris France 15 Unite Immunogenet, F-75724 Paris 15, France Inst Pasteur, Unite Biochim Cellulaire, F-75015 Paris, France Inst Pasteur Paris France F-75015 chim Cellulaire, F-75015 Paris, France Inst Pasteur, Unite Biol Mol Express Genique, F-75015 Paris, France Inst Pasteur Paris France F-75015 Express Genique, F-75015 Paris, France INSERM, U461, F-92296 Chatenay Malabry, France INSERM Chatenay Malabry France F-92296 F-92296 Chatenay Malabry, France INSERM, U463, F-44000 Nantes, France INSERM Nantes France F-44000INSERM, U463, F-44000 Nantes, France Inst Pasteur, Unite Biochim Struct, F-72015 Paris, France Inst Pasteur Paris France F-72015 Biochim Struct, F-72015 Paris, France Inst Pasteur, F-59000 Lille, France Inst Pasteur Lille France F-59000Inst Pasteur, F-59000 Lille, France Inst Gustave Roussy, INSERM, U487, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France
Titolo Testata:
CELLULAR AND MOLECULAR BIOLOGY
fascicolo: 4, volume: 47, anno: 2001,
pagine: 703 - 707
SICI:
0145-5680(200106)47:4<703:COAIMW>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-BETA-CHAIN; HUMAN INTERLEUKIN-2 RECEPTOR; ALPHA-CHAIN; GAMMA-CHAIN; HIGH-AFFINITY; BINDING; EXPRESSION; CELLS; IDENTIFICATION; CYTOKINE;
Keywords:
IL-2 mimetic; synthetic hemopoietin; dimeric IL-2R beta; signal transduction; NK-cells;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Theze, J Inst Pasteur, Dept Immunol, Unite Immunogenet, 25-28 Rue Dr Roux,F-75724 Paris 15, France Inst Pasteur 25-28 Rue Dr Roux Paris France 15 Paris 15, France
Citazione:
R. Eckenberg et al., "Characterization of an IL-2 mimetic with therapeutic potential", CELL MOL B, 47(4), 2001, pp. 703-707

Abstract

Human interleukin-2 (IL-2) interacts with two types of functional receptors (IL-2R alpha beta gamma and IL-2R beta gamma) 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 mimickingthe quaternary structure of an hemopoietin. Indeed, peptide p1-30 (containing amino acids 1 to 30, including the sequence corresponding to the entirea helix A of IL-2) spontaneously folds into an a-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. Atthe 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 productionis 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 13:08:43