A mutant cell with a novel defect in MHC class I quality control.
J Immunol
; 174(11): 6839-46, 2005 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-15905525
ABSTRACT
COS7 (African Green Monkey kidney) cells stably transfected with the mouse MHC class I allele H-2K(b) were mutagenized, selected for low surface expression of endogenous MHC class I products, and subcloned. A mutant cell line, 4S8.12, expressing very low surface MHC class I (approximately 5% of parental levels) was identified. This cell line synthesized normal levels of the MHC class I H chain and beta(2)-microglobulin, as well as normal levels of TAP, tapasin, GRP78, calnexin, calreticulin, ERp57, and protein disulfide isomerase. Full-length OVA was processed to generate presented H-2K(b)-SIINFEKL complexes with equal efficiency in wild-type and mutant cells, demonstrating that proteasomes, as well as TAP and tapasin, functioned normally. Therefore, all the known components of the MHC class I Ag presentation pathway were intact. Nevertheless, primate (human and monkey) MHC class I H chain and beta(2)-microglobulin failed to associate to form the normal peptide-receptive complex. In contrast, mouse H chains associated with beta(2)-microglobulin normally and bound peptide at least as well as in wild-type cells. The 4S8.12 cells provide strong genetic evidence for a novel component in the MHC class I pathway. This as-yet unidentified gene is important in early assembly of primate, but not mouse, MHC class I complexes.
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Base de dados:
MEDLINE
Assunto principal:
Antígenos H-2
/
Regulação para Baixo
/
Processamento de Proteína Pós-Traducional
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Mutagênese
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article