Soluble MHC-peptide complexes containing long rigid linkers abolish CTL-mediated cytotoxicity.

Détails

ID Serval
serval:BIB_8E2DE96E14F3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Soluble MHC-peptide complexes containing long rigid linkers abolish CTL-mediated cytotoxicity.
Périodique
Journal of immunology
Auteur(s)
Angelov G.S., Guillaume P., Cebecauer M., Bosshard G., Dojcinovic D., Baumgaertner P., Luescher I.F.
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
176
Numéro
6
Pages
3356-3365
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Soluble MHC-peptide (pMHC) complexes induce intracellular calcium mobilization, diverse phosphorylation events, and death of CD8+ CTL, given that they are at least dimeric and co-engage CD8. By testing dimeric, tetrameric, and octameric pMHC complexes containing spacers of different lengths, we show that their ability to activate CTL decreases as the distance between their subunit MHC complexes increases. Remarkably, pMHC complexes containing long rigid polyproline spacers (> or =80 A) inhibit target cell killing by cloned S14 CTL in a dose- and valence-dependent manner. Long octameric pMHC complexes abolished target cell lysis, even very strong lysis, at nanomolar concentrations. By contrast, an altered peptide ligand antagonist was only weakly inhibitory and only at high concentrations. Long D(b)-gp33 complexes strongly and specifically inhibited the D(b)-restricted lymphocytic choriomeningitis virus CTL response in vitro and in vivo. We show that complications related to transfer of peptide from soluble to cell-associated MHC molecules can be circumvented by using covalent pMHC complexes. Long pMHC complexes efficiently inhibited CTL target cell conjugate formation by interfering with TCR-mediated activation of LFA-1. Such reagents provide a new and powerful means to inhibit Ag-specific CTL responses and hence should be useful to blunt autoimmune disorders such as diabetes type I.
Mots-clé
Animals, Calcium/metabolism, Cell Adhesion, Cell Death, Cells, Cultured, Cross-Linking Reagents/chemistry, Cytotoxicity, Immunologic/immunology, Dimerization, Histocompatibility Antigens/chemistry, Histocompatibility Antigens/immunology, Lymphocyte Function-Associated Antigen-1/metabolism, Mice, Peptide Fragments/chemistry, Peptide Fragments/metabolism, Peptides/chemistry, Protein Binding, Solubility, T-Lymphocytes, Cytotoxic/cytology, T-Lymphocytes, Cytotoxic/immunology
Pubmed
Web of science
Création de la notice
28/01/2008 12:20
Dernière modification de la notice
03/03/2018 19:18
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