Molecular mechanism and cellular function of MHCII ubiquitination.
Immunol Rev
; 266(1): 134-44, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-26085212
ABSTRACT
The major histocompatibility complex class II (MHCII) is ubiquitinated via the evolutionarily conserved lysine in the cytoplasmic tail of the ß chain in dendritic cells (DCs) and B cells. The ubiquitination is mediated by the membrane-associated RING-CH1 (MARCH1) ubiquitin ligase although it can be also mediated by the homologous ligase MARCH8 in model cell lines. The ubiquitination promotes MHCII endocytosis and lysosomal sorting that results in a reduction in the level of MHCII at cell surface. Functionally, MHCII ubiquitination serves as a means by which DCs suppress MHCII expression and reduce antigen presentation in response to the immune regulatory cytokine interleukin-10 (IL-10) and regulatory T cells. Recently, additional roles of MHCII ubiquitination have emerged. MHCII ubiquitination promoted DC production of inflammatory cytokines in response to the Toll-like receptor ligands. It also potentiated DC ability to activate antigen-specific naive CD4(+) T cells while limiting the amount of antigens presented at cell surface. Similarly, MHCII ubiquitination promoted DC activation of CD4(+) thymocytes supporting regulatory T-cell development independent of its effect of limiting antigen presentation. Thus, ubiquitination appears to confer MHCII a function independent of presenting antigens by a mechanism yet to be identified.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Antígenos de Histocompatibilidade Classe II
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Ubiquitinação
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article