title: αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands.
abstract: A central paradigm in αβ T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the αβ T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A' roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby αβ T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.
authors: 1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia. [2] ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia.
authors: Richard W
authors: RW
authors: Birkinshaw
authors: 1] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia. [2] ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Australia.
authors: Daniel G
authors: DG
authors: Pellicci
authors: Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, Massachusetts, USA.
authors: Tan-Yun
authors: TY
authors: Cheng
authors: 1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia. [2] ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia.
authors: Andrew N
authors: AN
authors: Keller
authors: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia.
authors: Maria
authors: M
authors: Sandoval-Romero
authors: 1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia. [2] ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia.
authors: Stephanie
authors: S
authors: Gras
authors: Department of Dermatology, Columbia University, New York, New York, USA.
authors: Annemieke
authors: A
authors: de Jong
authors: 1] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia. [2] ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Australia.
authors: Adam P
authors: AP
authors: Uldrich
authors: Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, Massachusetts, USA.
authors: D Branch
authors: DB
authors: Moody
authors: 1] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia. [2] ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Australia.
authors: Dale I
authors: DI
authors: Godfrey
authors: 1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia. [2] ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Australia. [3] Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
authors: Jamie
authors: J
authors: Rossjohn
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008055:Lipids / Q000276:immunology*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D001324:Autoantigens; C419393:CD1a antigen; D008024:Ligands; D008055:Lipids; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta
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