Stimulation of an unfolded protein response impairs MHC class I expression

• Type: Article in International Scientific Journal
• Date: 2007

Authors

de almeida, sf (Author) Other; fleming, jv (Author) Other; azevedo, je (Author) ICBAS; carmo-fonseca, m (Author) Other; de sousa, m (Author) Other

Journal

Title: Journal of Immunology

Vol. 178

Pages: 3612-3619

ISSN: 0022-1767

Publisher: American Association of Immunologists

Indexing

ISI Web of Knowledge - 27 Citations

Scopus - 29 Citations

Other information

Authenticus ID: P-004-B5T

Abstract (EN): HFE C282Y is an example of a mutant protein that does not fold correctly, is retained in the endoplasmic reticulum, and was found previously to diminish surface expression of MHC class I (MHC-I). We now show that its expression in 293T cells triggers an unfolded protein response (UPR), as revealed by the increased levels of H chain binding protein, GRP94, and C/EBP homologous protein. Elevated levels of these proteins were also found in HFE C282Y homozygous PBMCs. Following the UPR induction, a decrease in MHC-I cell surface expression was observed. This defect in MHC-I could be mimicked, however, by overexpression of transcriptionally active isoforms of activating transcription factor-6 and X box-binding protein-1, which induced the UPR, and reversed in HFE C282Y-expressing cells by using dominant-negative constructs that block UPR signaling. The present results provide evidence to the finding that stimulation of an UPR affects MHC-I expression.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8