title: Direct recognition by alphabeta cytolytic T cells of Hfe, a MHC class Ib molecule without antigen-presenting function.
abstract: Crystallographic analysis of human Hfe has documented an overall structure similar to classical (class Ia) MHC molecules with a peptide binding groove deprived of ligand. Thus, to address the question of whether alphabeta T cells could recognize MHC molecules independently of bound ligands, we studied human and mouse Hfe interactions with T lymphocytes. We provide formal evidence of direct cytolytic recognition of human Hfe by mouse alphabeta T cell receptors (TCR) in HLA-A*0201 transgenic mice and that this interaction results in ZAP-70 phosphorylation. Furthermore, direct recognition of mouse Hfe molecules by cytotoxic T lymphocytes (CTLs) was demonstrated in DBA/2 Hfe knockout mice. These CTLs express predominantly two T cell antigen receptor alpha variable gene segments (AV6.1 and AV6.6). Interestingly, in wild-type mice we identified a subset of CD8+ T cells positively selected by Hfe that expresses the AV6.1/AV6.6 gene segments. T cell antigen receptor recognition of MHC molecules independently of bound ligand has potential general implications in alloreactivity and identifies in the Hfe case a cognitive link supporting the concept that the immune system could be involved in the control of iron metabolism.
authors.affiliation: Unité d'Immunité Cellulaire Antivirale, Département d'Immunologie, Institut Pasteur, 75724 Paris, France.
authors.forename: Pierre S
authors.initials: PS
authors.lastname: Rohrlich
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fazilleau
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Firat
authors.forename: Frédérique
authors.initials: F
authors.lastname: Michel
authors.forename: Madeleine
authors.initials: M
authors.lastname: Cochet
authors.forename: Nihay
authors.initials: N
authors.lastname: Laham
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Roth
authors.forename: Steve
authors.initials: S
authors.lastname: Pascolo
authors.forename: Faridabano
authors.initials: F
authors.lastname: Nato
authors.forename: Hélène
authors.initials: H
authors.lastname: Coppin
authors.forename: Pierre
authors.initials: P
authors.lastname: Charneau
authors.forename: Olivier
authors.initials: O
authors.lastname: Danos
authors.forename: Oreste
authors.initials: O
authors.lastname: Acuto
authors.forename: Rachel
authors.initials: R
authors.lastname: Ehrlich
authors.forename: Jean
authors.initials: J
authors.lastname: Kanellopoulos
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002460:Cell Line; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell