Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes

Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding...

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Detalles Bibliográficos
Autores: Reche Gallardo, Pedro Antonio, Keskin, Derin B, Hussey, Rebecca E, Ancuta, Petronela, Gabuzda, Dana, Reinherz, Ellis L
Tipo de recurso: artículo
Fecha de publicación:2006
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/50380
Acceso en línea:https://hdl.handle.net/20.500.14352/50380
Access Level:acceso abierto
Palabra clave:612.017
57:004
Inmunología
Microbiología (Biología)
Biología molecular (Biología)
Bioinformática
2412 Inmunología
2414 Microbiología
2415 Biología Molecular
Descripción
Sumario:Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding predictions with knowledge concerning HLA allele frequencies, a metric estimating population protection coverage (PPC) was computed and epitope pools assembled. Strikingly, only a minority of immunocompetent HIV-1 infected individuals responds to pools with PPC >95%. In contrast, virus-naive individuals uniformly expand IFNgamma producing cells and mount anti-HIV-1 cytolytic activity. This disparity suggests a vaccine design paradigm shift from infected to normal subjects.