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 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.
López-Moratalla
N
N
Department of Biochemistry, University of Navarra, Pamplona, Spain.
López-Zabalza
M J
MJ
Subirá
M L
ML
Borrás-Cuesta
F
F
Pérez-Mediavilla
L A
LA
Santiago
E
E
D000595:Amino Acid Sequence; D000954:Antigens, Surface / Q000032:analysis; D016923:Cell Death; D002478:Cells, Cultured / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000097:blood; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000954:Antigens, Surface; D007375:Interleukin-1; D010455:Peptides; D013205:Staphylococcal Protein A; D014409:Tumor Necrosis Factor-alpha