biostudies-literatureUnknown102(36)Rohrlich PSCrystallographic 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.Proceedings of the National Academy of Sciences of the United States of America12855-60https://www.ebi.ac.uk/biostudies/studies/S-EPMC1200262biostudies-literatureDirect recognition by alphabeta cytolytic T cells of Hfe, a MHC class Ib molecule without antigen-presenting function.PMC1200262Charneau PFazilleau NPascolo SCoppin HRohrlich PSLemonnier FARoth MPLaham NMichel FGinhoux FNato FDanos OCochet MAcuto OEhrlich RKanellopoulos JFirat HfalseDirect recognition by alphabeta cytolytic T cells of Hfe, a MHC class Ib molecule without antigen-presenting function.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 AV6.2005-01-01T00:00:00Z2005 Sep2025-04-05T11:22:08.525Z2019-03-27T01:09:20ZS-EPMC12002621612313610.1073/pnas.0502309102