期刊
FASEB JOURNAL
卷 19, 期 6, 页码 1190-+出版社
WILEY
DOI: 10.1096/fj.04-3498fje
关键词
transmembrane domain assembly; peptide inhibitor; immunosuppression; protein-protein interaction
T cell activation requires the cross-talk between the CD3-signaling complex and the T cell receptor (TCR). A synthetic peptide coding for the TCR alpha. transmembrane domain (CP) binds CD3 molecules, interferes with the CD3/TCR cross-talk, and inhibits T cell activation. Intermolecular interactions are sterically constrained; accordingly no sequence-specific interactions are thought to occur between D- and L-stereoisomers. This argument was recently challenged when applied to intra-membrane protein assembly. In this paper we studied the ability of a D-stereoisomer of CP (D-CP) to inhibit T cell activation. L-CP and D-CP co-localized with the TCR in the membrane and inhibited T cell activation in a sequence-specific manner. In vivo, both L-CP and D-CP inhibited adjuvant arthritis. In molecular terms, these results suggest the occurrence of structural reorientation that facilitates native-like interactions between D-CP and CD3 within the membrane. In clinical terms, our results demonstrate that D-stereoisomers retain the therapeutic properties of their L-stereoisomers, while they benefit from an increased resistance to degradation.
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