Open AccessRational design of biologically active peptides: inhibition of T cell activation through interference with CD 4 function
Author(s) -
Pozzetto U.,
Facchiano A.,
Serino F.
Publication year - 2000
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2000.tb02046.x
Subject(s) - peptide , stimulation , receptor , intracellular , cell culture , function (biology) , mechanism of action , cell , microbiology and biotechnology , pharmacology , medicine , biochemistry , in vitro , chemistry , biology , genetics
In our laboratory we generated one synthetic cyclic peptide (Pep4) and tested it in human mitogen stimulation assays (MSA) and mixed lymphocytes reactions (MLR) generating dose‐response curves showing a dose‐dependent inhibition of MSA up to 80% and MLR up to 98%. MSA and MLR were repeated after pre incubation of the Pep 4 with each separate responder cell subset and subsequent reconstitution: these experiments showed inhibition only when the peptide was present in culture. Pep 4 showed species specificity since it was ineffective in inhibiting rat MLR. Combination effect analysis with Pep 4 and cyclosporine showed a combination index > 1. This rationally designed peptide (Pep 4 ) shows powerful inhibition of human T cell activation and, although the exact mechanism is still undefined, it seems to exert its major action on the T cell surface, interfering with co receptor interaction and disrupting the same activation signal pathway inhibited by cyclosporine A.