Silencing an immunodominant epitope of hepatitis B surface antigen reveals an alternative repertoire of CD8 T cell epitopes of this viral antigen.
Vaccine
; 28(1): 114-9, 2009 Dec 10.
Article
em En
| MEDLINE
| ID: mdl-19818719
ABSTRACT
Immunodominance hierarchies operating in immune responses to viral antigens limit the diversity of the elicited T cell responses. The L(d)/S(28-39)-restricted CD8 T cell response to the hepatitis B surface antigen (HBsAg or S) prevents copriming of D(d)- and K(b)-restricted CD8 T cell responses. We exchanged L to V at position S(39) of HBsAg to construct mutant S(L39V). Comparable levels of wild-type S and mutant S(L39V) were produced by transiently transfected cells, and mice immunized with the pCI/S and pCI/S(L39V) DNA vaccines showed comparable serum antibody responses to HBsAg. The pCI/S but not pCI/S(L39V) DNA vaccination induced L(d)/S(28-39)-specific CD8 T cell responses. However, the pCI/S(L39V) DNA vaccine efficiently primed CD8 T cell responses to the subdominant D(d)- and K(b)-restricted epitopes, confirming the immunosuppressive phenotype of the L(d)/S(28-39)-specific CD8 T cell response. A single point mutation within the HBsAg can hence completely silence a 'dominant' CD8 T cell response thereby facilitating priming of a multispecific repertoire of suppressed, 'subdominant' epitopes. The data have practical implications for understanding HBV-specific CD8 T cell responses and for the design of novel vaccination strategies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Epitopos Imunodominantes
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Vacinas contra Hepatite B
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Antígenos de Superfície da Hepatite B
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article