Early lymphocyte activation events are inhibited by antiproliferative synthetic peptide 2438, a fragment of human interferon alpha-2, and immunosuppressant cyclosporine A.
A synthetic peptide (designated 2438) corresponding to the human interferon alpha-2 amino acid sequence 124-138 inhibits proliferation of T-lymphocytes in vitro. Time-course experiments suggest that peptide 2438 affects early stages of lymphocyte activation. Molecular mechanisms of peptide 2438 action were studied. By western-blotting with monoclonal antibodies against phosphotyrosine peptide 2438 was shown to decrease the phosphotyrosine content of an endogenous protein substrate (M.M. = 36 kDa) in human lymphocytes activated with concanavalin A (ConA). Similar effect on tyrosine-specific phosphorylation in mitogen-stimulated lymphocytes was observed with the native interferon or Cyclosporine A (CsA). Calcium fluxes induced by ConA in human lymphocytes were measured using a fluorescent calcium chelator Fura-2. In contrast to CsA, peptide 2438 did not affect the ConA-induced calcium influx in lymphocytes.
Freze
K V
KV
Department of Cell Physiology and Immunology, Biological Faculty, Moscow State University, Russia.
Danilkovich
A V
AV
Kharitonenkov
A I
AI
Shevalier
A F
AF
Surin
A M
AM
Khodorova
A B
AB
Astashkin
E I
EI
Bulargina
T V
TV
D002118:Calcium / Q000378:metabolism; D003208:Concanavalin A; D016572:Cyclosporine / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D013601:T-Lymphocytes / Q000166:cytology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016898:Interferon-alpha; D010446:Peptide Fragments; D010750:Phosphoproteins; C090879:peptide 2438; D003208:Concanavalin A; D019000:Phosphotyrosine; D014443:Tyrosine; D016572:Cyclosporine; D007372:Interferons; D002118:Calcium