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Coreceptor-independent T cell activation in mice expressing MHC class II molecules mutated in the CD4 binding domain.
Mostaghel, E A; Riberdy, J M; Steeber, D A; Doyle, C.
Afiliación
  • Mostaghel EA; Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol ; 161(12): 6559-66, 1998 Dec 15.
Article en En | MEDLINE | ID: mdl-9862682
We have previously reported that efficient selection of the mature CD4+ T cell repertoire requires a functional interaction between the CD4 coreceptor on the developing thymocyte and the MHC class II molecule on the thymic epithelium. Mice expressing a class II protein carrying the EA137/VA142 double mutation in the CD4 binding domain develop fewer than one-third the number of CD4+ T cells found in wild-type mice. In this report we describe the functional characteristics of this population of CD4+ T cells. CD4+ T cells that develop under these conditions are predicted to be a CD4-independent subset of T cells, bearing TCRs of sufficient affinity for the class II ligand to undergo selection despite the absence of accessory class II-CD4 interactions. We show that CD4+ T cells from the class II mutant mice are indeed CD4 independent in their peripheral activation requirements. Surprisingly, we find that CD4+ T cells from the class II mutant mice, having been selected in the absence of a productive class II-CD4 interaction, fail to functionally engage CD4 even when subsequently provided with a wild-type class II ligand. Nevertheless, CD4+ T cells from EA137/VA142 class II mutant mice can respond to T-dependent Ags and support Ig isotype switching.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T CD4-Positivos / Antígenos de Histocompatibilidad Clase II / Antígenos CD4 / Subgrupos de Linfocitos T Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 1998 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T CD4-Positivos / Antígenos de Histocompatibilidad Clase II / Antígenos CD4 / Subgrupos de Linfocitos T Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 1998 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos