TY - JOUR
TI - Prothymosin α immunoactive carboxyl-terminal peptide TKKQKTDEDD stimulates lymphocyte reactions, induces dendritic cell maturation and adopts a β-sheet conformation in a sequence-specific manner
AU - Skopeliti, M.
AU - Iconomidou, V.A.
AU - Derhovanessian, E.
AU - Pawelec, G.
AU - Voelter, W.
AU - Kalbacher, H.
AU - Hamodrakas, S.J.
AU - Tsitsilonis, O.E.
JO - Cellular and Molecular Immunology
PY - 2009
VL - 46
TODO - 5
SP - 784-792
PB - 
SN - null
TODO - 10.1016/j.molimm.2008.09.014
TODO - amyloid;  caspase;  polypeptide;  prothymosin alpha;  prothymosin alpha[100-109];  synthetic peptide;  threonyllysyllysylglutaminyllysylthreonylaspartylglutamylaspartylaspartic acid;  unclassified drug, amino acid sequence;  apoptosis;  article;  beta sheet;  blood donor;  carboxy terminal sequence;  cell function;  cell isolation;  cell maturation;  controlled study;  cytotoxicity;  dendritic cell;  human;  human cell;  immune response;  immunoreactivity;  in vivo study;  infrared spectroscopy;  long terminal repeat;  lymphocyte;  lymphocyte activation;  lymphocyte function;  monocyte;  natural killer cell;  normal human;  nuclear localization signal;  peripheral blood mononuclear cell;  priority journal;  protein analysis;  protein cleavage;  protein conformation;  protein synthesis;  sequence analysis;  sequence homology;  transmission electron microscopy, Amyloid;  Apoptosis;  Caspases;  Cells, Cultured;  Dendritic Cells;  Humans;  Lymphocytes;  Monocytes;  Peptides;  Protein Precursors;  Protein Structure, Secondary;  Thymosin;  Toll-Like Receptors
TODO - Prothymosin α (ProTα) is a small acidic polypeptide with important immunostimulatory properties, which we have previously shown to be exerted by its carboxyl (C)-terminus. It exerts immunoenhancing effects through stimulation of monocytes via toll-like receptor (TLR) triggering. Here, we assayed the activity of synthetic peptides homologous to ProTα's C-terminus to stimulate lymphocyte functions, in particular natural killer cell cytotoxicity of peripheral blood mononuclear cells isolated from healthy donors. A synthetic decapeptide TKKQKTDEDD was identified as the most potent lymphocyte stimulator. The activity of this peptide was sequence-specific and comparable to that of the intact molecule, suggesting that ProTα's immunoactive segment encompasses the nuclear localization signal sequence of the polypeptide. Because ProTα stimulates immune responses in a monocyte-dependent manner, we further investigated whether the entire molecule and its peptide TKKQKTDEDD specifically act on monocytes and show that both can promote maturation of monocyte-derived dendritic cells (DC). Finally, knowing that, under specific conditions, ProTα forms amyloid fibrils, we studied the amyloidogenic properties of its C-terminal peptide segments, utilizing ATR FT-IR spectroscopy and transmission electron microscopy (negative staining). Although the peptide TKKQKTDEDD adopts an antiparallel β-sheet conformation under various conditions, it does not form amyloid fibrils; rather it aggregates in globular particles. These data, in conjunction with reports showing that the peptide TKKQKTDEDD is generated in vivo upon caspase-cleavage of ProTα during apoptosis, strengthen our hypothesis that immune response stimulation by ProTα is in principle exerted via its bioactive C-terminal decapaptide, which can acquire a sequence-specific β-sheet conformation and induce DC maturation. © 2008 Elsevier Ltd. All rights reserved.
ER -