Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses.

Détails

Ressource 1Télécharger: PLoS ONE 2017 Spodzieja.pdf (3856.90 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_8C02B51C71F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses.
Périodique
PloS one
Auteur(s)
Spodzieja M., Lach S., Iwaszkiewicz J., Cesson V., Kalejta K., Olive D., Michielin O., Speiser D.E., Zoete V., Derré L., Rodziewicz-Motowidło S.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2017
Volume
12
Numéro
6
Pages
e0179201
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Antibody based immune-checkpoint blockade therapy is a major breakthrough in oncology, leading to clinical benefit for cancer patients. Among the growing family of inhibitory receptors, the B and T lymphocyte attenuator (BTLA), which interacts with herpes virus entry mediator (HVEM), is a promising target for immunotherapy. Indeed, BTLA inhibits T-cell proliferation and cytokine production. The crystal structure of the BTLA/HVEM complex has shown that the HVEM(26-38) fragment is directly involved in protein binding. We designed and analyzed the capacity of several analogs of this fragment to block the ligation between BTLA and HVEM, using competitive ELISA and cellular assay. We found that the HVEM(23-39) peptide can block BTLA/HVEM ligation. However, the blocking ability was due to the Cys encompassed in this peptide and that even free cysteine targeted the BTLA protein and blocked its interaction with HVEM. These data highlight a Cys-related artefact in vitro, which should be taken in consideration for future development of BTLA/HVEM blocking compounds.

Pubmed
Web of science
Création de la notice
28/06/2017 14:24
Dernière modification de la notice
03/03/2018 19:12
Données d'usage