Mammalian target of rapamycin complex 2 modulates αßTCR processing and surface expression during thymocyte development.
J Immunol
; 193(3): 1162-70, 2014 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-24981454
ABSTRACT
An efficient immune response relies on the presence of T cells expressing a functional TCR. Whereas the mechanisms generating TCR diversity for antigenic recognition are well defined, what controls its surface expression is less known. In this study, we found that deletion of the mammalian target of rapamycin complex (mTORC) 2 component rictor at early stages of T cell development led to aberrant maturation and increased proteasomal degradation of nascent TCRs. Although CD127 expression became elevated, the levels of TCRs as well as CD4, CD8, CD69, Notch, and CD147 were significantly attenuated on the surface of rictor-deficient thymocytes. Diminished expression of these receptors led to suboptimal signaling, partial CD4(-)CD8(-) double-negative 4 (CD25(-)CD44(-)) proliferation, and CD4(+)CD8(+) double-positive activation as well as developmental blocks at the CD4(-)CD8(-) double-negative 3 (CD25(+)CD44(-)) and CD8-immature CD8(+) single-positive stages. Because CD147 glycosylation was also defective in SIN1-deficient fibroblasts, our findings suggest that mTORC2 is involved in the co/posttranslational processing of membrane receptors. Thus, mTORC2 impacts development via regulation of the quantity and quality of receptors important for cell differentiation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T
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Proteínas Portadoras
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Procesamiento Proteico-Postraduccional
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Receptores de Antígenos de Linfocitos T alfa-beta
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Regulación del Desarrollo de la Expresión Génica
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Complejos Multiproteicos
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Serina-Treonina Quinasas TOR
Límite:
Animals
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Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article