Cytotoxic T lymphocyte responses to wild-type and mutant mouse p53 peptides

Détails

ID Serval
serval:BIB_D110C49D9369
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cytotoxic T lymphocyte responses to wild-type and mutant mouse p53 peptides
Périodique
European Journal of Immunology
Auteur(s)
Bertholet  S., Iggo  R., Corradin  G.
ISSN
0014-2980 (Print)
Statut éditorial
Publié
Date de publication
03/1997
Volume
27
Numéro
3
Pages
798-801
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Résumé
Cytotoxic T lymphocytes (CTL) recognize peptides presented at the cell surface in association with major histocompatibility complex (MHC) class I molecules. The finding that peptides binding to MHC class I molecules share common amino acid motifs renders feasible the selection of antigenic peptides by simply scanning protein sequences, and thus, provides the possibility of inducing CTL to pre-defined specificities. Tumor cells possess antigens known to generate MHC class I-restricted CD8+ CTL responses. Thus, these antigens represent good targets to induce tumor-specific immunity. Among these antigens, the p53 tumor suppressor gene product is an attractive candidate for cancer immunotherapy. Mutations in the p53 gene have been found to be very frequently associated with a malignant transformation and often lead to p53 protein overexpression. Thus, we investigated the possibility of inducing CTL to wild-type or mutant p53 peptides in a BALB/c (H-2d) mouse model. Peptides possessing the H2-Kd binding motif were selected and tested for binding to the H-2Kd molecules in vitro. Synthetic peptides p53(122-130) wild-type or "mutant" (Lys --> Glu substitution at position 129) were shown to be the best binder peptides and were tested for their immunogenicity in mice. H-2Kd-restricted p53-specific CD8+ CTL were generated following immunization of mice with either wild-type (wt) p53(122-130) or mutant (mut) p53(122-130) (E129) peptides. Only low-affinity CTL can be obtained by immunization with the wt sequence. In contrast, CTL elicited with the mut peptide recognized the mut sequence at a 10-100-fold lower concentration. This indicates that CTL elicited with the mut peptide recognized the mut sequence very efficiently, whereas the wt sequence is poorly recognized, if at all. Taken together, these results thus suggest that p53-specific tumor immunotherapy may be successful only if the mutated protein is taken into consideration.
Mots-clé
Animals Binding, Competitive Cells, Cultured Cytotoxicity, Immunologic H-2 Antigens/immunology Mice Mice, Inbred BALB C Peptides/immunology Structure-Activity Relationship T-Lymphocytes, Cytotoxic/*immunology Tumor Suppressor Protein p53/*immunology
Pubmed
Web of science
Création de la notice
24/01/2008 14:55
Dernière modification de la notice
20/08/2019 15:51
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