Human invariant chain isoform p35 restores thymic selection and antigen presentation in CD74-deficient mice.
Immunol Cell Biol
; 90(9): 896-902, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22689013
ABSTRACT
The invariant chain (Ii) has pleiotropic functions and is a key factor in antigen presentation. Ii associates with major histocompatibility complex class II molecules in the endoplasmic reticulum (ER) and targets the complex in the endocytic pathway to allow antigenic peptide loading. The human Iip35 isoform includes a cytoplasmic extension containing a di-arginine motif causing ER retention. This minor isoform does not exist in mice and its function in humans has not been thoroughly investigated. We have recently generated transgenic mice expressing Iip35 and these were crossed with Ii-deficient mice to generate animals (Tgp35/mIiKO) expressing exclusively the human isoform. In these mice, we show that Iip35 is expressed in antigen presenting cells and is inducible by interferon gamma (IFN-γ). Despite the low constitutive expression of the protein and some minor differences in the Vß repertoire of Tgp35/mIiKO mice, Iip35 restored thymic selection of CD4(+) T cells and of invariant natural killer T cells. In vitro functional assays using purified primary macrophages treated with IFN-γ showed that Iip35 allows presentation of an Ii-dependent ovalbumin T-cell epitope. Altogether, our results suggest that Iip35 is functional and does not require co-expression of other isoforms for antigen presentation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timo
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Antígenos de Diferenciação de Linfócitos B
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Antígenos de Histocompatibilidade Classe II
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Apresentação de Antígeno
Idioma:
En
Revista:
Immunol Cell Biol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá