A COMMON STRUCTURAL MOTIF IN IMMUNOPOTENTIATING PEPTIDES WITH SEQUENCES PRESENT IN HUMAN AUTOANTIGENS - ELICITATION OF A RESPONSE MEDIATED BY MONOCYTES AND TH1 CELLS
N. Lopezmoratalla et al., A COMMON STRUCTURAL MOTIF IN IMMUNOPOTENTIATING PEPTIDES WITH SEQUENCES PRESENT IN HUMAN AUTOANTIGENS - ELICITATION OF A RESPONSE MEDIATED BY MONOCYTES AND TH1 CELLS, Biochimica et biophysica acta. Molecular basis of disease, 1317(3), 1996, pp. 183-191
We have found a common structural motif in human autoantigens, heat sh
ock proteins and viral proteins. Peptides modelled after sequences pre
sent in those molecules were synthesized and immunomodulating properti
es tested. They share a core of 15 amino acid residues and a common pa
ttern ('2-6-11' motif) characterized by requirements at fixed position
s with respect to a Pro (position 6); an apolar residue or a Lys at po
sition 2; and a Glu, Asp or Lys at position 11. Anp of these peptides,
when added to cultures of lymphomononuclear cells, caused the activat
ion 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 relea
se 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 f
rom 12 patients of Graves' disease, 8 of Hashimoto's disease and 8 of
primary biliary cirrhosis exhibited activation features similar to tho
se found in cells from healthy subjects incubated in the presence of p
eptides with a '2-6-11' motif and representing fragments of autoantige
ns. Their immunopotentiating properties suggest their involvement in t
he initiation or progression of the autoimmune response mediated by ac
tivated monocytes and Th1 cells.