T-cell antigen receptor peptides inhibit signal transduction within the membrane bilayer
Previous studies have shown that a synthetic peptide (core peptide, CP) corresponding to a 9-amino-acid region in the transmembrane domain of the alpha subunit of the T-cell antigen receptor (TCR) can suppress T-cell function in vitro and in vivo. The aim of these experiments was to determine the ce...
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 105(2002), 2 vom: 01. Nov., Seite 199-207 |
|---|---|
| Auteur principal: | |
| Autres auteurs: | , , , , , |
| Format: | Article |
| Langue: | English |
| Publié: |
2002
|
| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article CD3 Complex Cross-Linking Reagents Cytochrome c Group Interleukin-2 Lipid Bilayers Membrane Proteins Receptors, Antigen, T-Cell antigen T cell receptor, zeta chain core protein, human plus... |
| Résumé: | Previous studies have shown that a synthetic peptide (core peptide, CP) corresponding to a 9-amino-acid region in the transmembrane domain of the alpha subunit of the T-cell antigen receptor (TCR) can suppress T-cell function in vitro and in vivo. The aim of these experiments was to determine the cellular site and molecular mechanism of CP inhibition in T cells. The cytochrome c-sensitive TCR-expressing hybridoma (2B4) was stimulated with pigeon cytochrome c antigen, anti-CD3 crosslinking, or PMA and ionomycin, in the presence or absence of CP, and the resulting IL-2 produced was measured in a bioassay using an IL-2-dependent cell line (CTLL-2). In the presence of CP, IL-2 production was inhibited following antigen-induced stimulation. By contrast, when stimulated with cross-linking antibodies to the CD3 complex or with PMA and ionomycin, both of which activate T cells downstream of the TCR antigen recognition site, CP had no effect on IL-2 production. These experiments suggest that CP interferes with TCR function by inhibiting T-cell activation at the transmembrane/receptor level. In addition, we show that CP inhibits early TCR signal transduction events such as TCR zeta chain phosphorylation following stimulation with either antigen or anti-CD3-crosslinking antibodies, although this is unlikely to be the mechanism leading to the reduced IL-2 production |
|---|---|
| Description: | Date Completed 15.01.2003 Date Revised 06.11.2019 published: Print Citation Status MEDLINE |
| ISSN: | 1521-7035 |