N. Manolios et al., T-CELL ANTIGEN RECEPTOR TRANSMEMBRANE PEPTIDES MODULATE T-CELL FUNCTION AND T-CELL-MEDIATED DISEASE, Nature medicine, 3(1), 1997, pp. 84-88
Citations number
14
Categorie Soggetti
Medicine, Research & Experimental",Biology,"Cell Biology
This study describes a novel method of inhibiting T-cell function by t
he use of peptides rationally designed from the T-cell antigen recepto
r (TCR) alpha-chain transmembrane sequence involved with TCR receptor
assembly. The most effective peptide (core peptide, CP) modulating in
vitro and in vivo T-cell function contained nine amino acids two of wh
ich, lysine and arginine, were hydrophilic and separated by four hydro
phobic amino acids. CP without chemical modification or conjugation wa
s able to enter non-T and T cells. Conjugation of CP at the carboxyl t
erminus with palmitic acid resulted in a greater inhibition of cell in
terleukin-2 (IL-2) production in vitro than peptide alone. When examin
ed for effects in vivo, CP reduced clinical signs of inflammation in t
hree T cell-mediated disease models including adjuvant-induced arthrit
is, experimental allergic neuritis, and cyclophosphamide-induced diabe
tes in NOD/Lt(F) mice. This peptide or its analogues has potential as
a therapeutic agent in human inflammatory and autoimmune disorders.