A common structural motif in immunopotentiating peptides with sequences present in human autoantigens. Elicitation of a response mediated by monocytes and Th1 cells.
We have found a common structural motif in human autoantigens, heat shock proteins and viral proteins. Peptides modelled after sequences present in those molecules were synthesized and immunomodulating properties tested. They share a core of 15 amino acid residues and a common pattern ('2-6-11' motif) characterized by requirements at fixed positions with respect to a Pro (position 6); an apolar residue or a Lys at position 2; and a Glu, Asp or Lys at position 11. Any of these peptides, when added to cultures of lymphomononuclear cells, caused the activation of monocytes manifested by a release of IL-1 alpha, IL-1 beta and TNF alpha. A release of INF gamma and IL-2 took also place; this release was abolished by anti-DR antibodies. Neither IL-4 nor IL-5 could be detected. This suggests a presentation by APCs and the appearance of cells with a Th1 phenotype. Monocytes and Th1 cells freshly obtained from 12 patients of Graves' disease, 8 of Hashimoto's disease and 8 of primary biliary cirrhosis exhibited activation features similar to those found in cells from healthy subjects incubated in the presence of peptides with a "2-6-11' motif and representing fragments of autoantigens. Their immunopotentiating properties suggest their involvement in the initiation or progression of the autoimmune response mediated by activated monocytes and Th1 cells.
López-Moratalla
N
N
Department of Biochemistry, University of Navarra, Pamplona, Spain.
Ruíz
E
E
López-Zabalza
M J
MJ
Santiago
E
E
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry*; D001327:Autoimmune Diseases / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D001324:Autoantigens; D016207:Cytokines; D006360:Heat-Shock Proteins; D007375:Interleukin-1; D007376:Interleukin-2; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma