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Nat Immunol. 2015 Mar;16(3):258-66. doi: 10.1038/ni.3098. Epub 2015 Feb 2.

αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands.

Author information

1
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.
2
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.
3
Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia.
5
Department of Dermatology, Columbia University, New York, New York, USA.
6
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.

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.

PMID:
25642819
DOI:
10.1038/ni.3098
[Indexed for MEDLINE]

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