Protective efficacy of serially up-ranked subdominant CD8+ T cell epitopes against virus challenges.
PLoS Pathog
; 7(5): e1002041, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21625575
Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Epitopos Imunodominantes
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HIV-1
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Vacinas contra a AIDS
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article