High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.
Sci Rep
; 4: 4632, 2014 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-24755960
ABSTRACT
Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide epitopes is necessary for peptide-based vaccine strategies. We present a three-tiered strategy for identifying and validating immunogenic peptides first, identify peptides that form stable complexes with class I MHC molecules; second, determine whether cytotoxic T lymphocytes (CTLs) raised against the whole protein antigen recognize and lyse target cells pulsed with peptides that passed step 1; third, determine whether peptides that passed step 2, when administered in vivo as a vaccine in HLA-A2 transgenic mice, elicit CTLs that lyse target cells expressing the whole protein antigen. Our innovative approach uses dendritic cells transfected with Mtb antigen-encoding mRNA to drive antigen expression. Using this strategy, we have identified five novel peptide epitopes from the Mtb proteins Apa, Mtb8.4 and Mtb19.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Células Dendríticas
/
Antígenos de Histocompatibilidade Classe I
/
Mapeamento de Epitopos
/
Epitopos de Linfócito T
/
Ensaios de Triagem em Larga Escala
/
Mycobacterium tuberculosis
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article