T-CELL ANTIGEN RECEPTOR TRANSMEMBRANE PEPTIDES MODULATE T-CELL FUNCTION AND T-CELL-MEDIATED DISEASE

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.