The WT hemochromatosis protein HFE inhibits CD8+ T‐lymphocyte activation. Issue 6 (20th March 2014)

• Record Type: Journal Article
• Authors: Reuben, Alexandre; Phénix, Mikaël; Santos, Manuela M.; Lapointe, Réjean
• Is Part Of: European journal of immunology. Volume 44:Issue 6(2014:Jun.)
• Page Start: 1604
• Page End: 1614
• Publication Date: 2014-03-20
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201343955
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>MHC class I (MHC I) antigen presentation is a ubiquitous process by which cells present endogenous proteins to CD8⁺ T lymphocytes during immune surveillance and response. Hereditary hemochromatosis protein, HFE, is involved in cellular iron uptake but, while structurally homologous to MHC I, is unable to bind peptides. However, increasing evidence suggests a role for HFE in the immune system. Here, we investigated the impact of HFE on CD8⁺ T‐lymphocyte activation. Using transient HFE transfection assays in a model of APCs, we show that WT HFE (HFE_WT), but not C282Y‐mutated HFE, inhibits secretion of MIP‐1β from antigen‐specific CD8⁺ T lymphocytes. HFE_WT expression also resulted in major decreases in CD8⁺ T‐lymphocyte activation as measured by 4–1BB expression. We further demonstrate that inhibition of CD8⁺ T‐lymphocyte activation was independent of MHC I surface levels, β2‐m competition, HFE interaction with transferrin receptor, antigen origin, or epitope affinity. Finally, we identified the α1–2 domains of HFE_WT as being responsible for inhibiting CD8⁺ T‐lymphocyte activation. Our data imply a new role for HFE_WT in altering CD8⁺ T‐lymphocyte reactivity, which could modulate antigen immunogenicity.</p> </abstract>