| First Author | Wang XM | Year | 2002 |
| Journal | Clin Immunol | Volume | 105 |
| Issue | 2 | Pages | 199-207 |
| PubMed ID | 12482394 | Mgi Jnum | J:81135 |
| Mgi Id | MGI:2448113 | Doi | 10.1006/clim.2002.5270 |
| Citation | Wang XM, et al. (2002) T-cell antigen receptor peptides inhibit signal transduction within the membrane bilayer. Clin Immunol 105(2):199-207 |
| abstractText | 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. |
