Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A

Biochim Biophys Acta. 1994 Mar 31;1221(2):153-8. doi: 10.1016/0167-4889(94)90007-8.

Abstract

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity 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 increase of cytotoxicity against HT-29 cells. It was found that the active 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 any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Surface / analysis
  • Cell Death
  • Cells, Cultured / drug effects
  • Cytotoxicity, Immunologic* / drug effects
  • Humans
  • Interleukin-1 / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Molecular Sequence Data
  • Neoplasms / blood
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Staphylococcal Protein A / chemistry
  • Staphylococcal Protein A / pharmacology*
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Surface
  • Interleukin-1
  • Peptides
  • Staphylococcal Protein A
  • Tumor Necrosis Factor-alpha