HFE cross-talks with the MHC class I antigen presentation pathway

• Type: Article in International Scientific Journal
• Date: 2005

Authors

de almeida, sf (Author) Other; carvalho, if (Author) Other; cardoso, cs (Author) Other; cordeiro, jv (Author) Other; azevedo, je (Author) ICBAS; neefjes, j (Author) Other; de sousa, m (Author) Other

Journal

Title: Blood

Vol. 106

Pages: 971-977

ISSN: 0006-4971

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 45 Citations

Scopus - 47 Citations

Other information

Authenticus ID: P-000-20F

DOI: 10.1182/blood-2004-12-4640

Abstract (EN): HIFE is a protein known to be involved in iron metabolism; yet, other than its homology with major histocompatibility complex (MHC) class I molecules, it has not been described as having an immunologic function. Here we report that peripheral blood mononuclear cells (PBMCs) from patients with hereditary hemochromatosis (HH) carrying the C282Y mutation in HFE have reduced cell-surface expression of MHC class I due to an enhanced endocytosis rate of MHC class I molecules caused by premature peptide and beta(2)-Microglobulin dissociation. This faster turnover also leads to increased expression levels of cell-surface free class I heavy chains in mutant PBMCs. Biochemical analysis indicates an earlier peptide loading and endoplasmic reticulum maturation of MHC class I molecules in C282Y mutant cells. Thermostability assays further showed that in HIFE mutants the MHC class I peptide loading gives rise to low-stability heterotrimers that dissociate prematurely during its intracellular traffic. The present results suggest the existence of an intriguing cross-talk between a particular HIFE mutation and the classical MHC class I route. These findings constitute the first description of peptide presentation pathway abnormalities linked to HIFE and provide additional evidence for the occurrence of immunologic defects in patients with HH.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7