D-enantiomer peptide of the TCRα transmembrane domain inhibits T-cell activation in vitro and in vivo

Doron Gerber, Francisco J. Quintana, Itai Bloch, Irun R. Cohen, Yechiel Shai

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

T cell activation requires the cross-talk between the CD3-signaling complex and the T cell receptor (TCR). A synthetic peptide coding for the TCRalpha 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.
Original languageEnglish
Pages (from-to)1190-1192
Number of pages3
JournalFASEB Journal
Volume19
Issue number9
DOIs
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Dive into the research topics of 'D-enantiomer peptide of the TCRα transmembrane domain inhibits T-cell activation in vitro and in vivo'. Together they form a unique fingerprint.

Cite this