IMMUNOMODULATION INDUCED BY SYNTHETIC PEPTIDES DERIVED FROM STAPHYLOCOCCUS-AUREUS PROTEIN-A

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these pepti des, when present in cultures of lymphomononuclear cells from healthy donors-or from cancer patients (melanoma, breast carcinoma, non-Hodgki n lymphoma and renal cell carcinoma) promoted: (i) changes in the phen otype of the lymphomononuclear population, (ii) stimulation of monocyt es (release of IL-1 and TNF-(alpha), and (iii) an increase in cytotoxi city against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an in crease of cytotoxicity against HT-29 cells. It was found that the acti ve peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with a ny other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those requir ed for activity resulted in compounds with a marked decrease in the im munomodulating properties described, or lacking these properties altog ether.