Hck SH3 domain-dependent abrogation of Nef-induced class 1 MHC down-regulation.
Eur J Immunol
; 31(8): 2382-7, 2001 Aug.
Article
en En
| MEDLINE
| ID: mdl-11500821
ABSTRACT
The ability of specific virally encoded proteins to down-regulate MHC class I molecules may enable infected cells to elude killing by CTL. In the case of HIV-1, Nef appears to be responsible for this effect. Thus, interfering with Nef-induced MHC class I down-regulation would be a strategy for increasing HIV-1-specific CTL activity, particularly towards long-lived T cell populations such as memory T cells that harbor replication-competent virus. Here, using two Nef-expressing human cell model systems, we show that a dominant-negative mutant derived from the Hck protein-tyrosine kinase, composed of the Hck N-terminal region, as well as the SH3 and SH2 domains, was able to inhibit Nef-induced MHC class I molecule down-regulation. This effect was SH3 domain dependent as it was not evident when the cells were transfected with DN-Hck-W93F, an SH3 domain mutant. The inhibitory effect of dominant-negative-Hck (DN-Hck) on Nef-induced class I down-regulation suggests that this Nef-mediated effect requires an interaction between the Nef polyproline site and an SH3-containing cellular protein that is involved in MHC class I molecule turnover. Interfering with the function of the Nef SH3 binding site in this way represents a strategy for assisting the host CTL response to clear HIV-1-infected cells.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Antígenos de Histocompatibilidad Clase I
/
Regulación hacia Abajo
/
Productos del Gen nef
/
Proteínas Proto-Oncogénicas
/
VIH-1
/
Dominios Homologos src
Límite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Canadá