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

RW Birkinshaw; DG Pellicci; TY Cheng; AN Keller; M Sandoval-Romero; S Gras; A De Jong; AP Uldrich; DB Moody; DI Godfrey; J Rossjohn

Journal article

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

RW Birkinshaw, DG Pellicci, TY Cheng, AN Keller, M Sandoval-Romero, S Gras, A De Jong, AP Uldrich, DB Moody, DI Godfrey, J Rossjohn

Nature Immunology | Published : 2015

DOI: 10.1038/ni.3098

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 Aâ €2 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 recognit..

View full abstract

University of Melbourne Researchers

Richard Birkinshaw Author

Daniel Pellicci Author

Adam Uldrich Author

Dale Godfrey Author

Related Projects (4)

RESEARCH FELLOWSHIP

Professor Godfrey is an immunologist with a long standing history as a pioneer in the study of a specialised type of white blood cell, known..

IMMUNE REGULATION EFFECTOR FUNCTION AND THERAPY

We seek to understand how white blood cells detect and destroy disease, and how molecules of the immune system punch holes in diseased cells..

AN ADVANCED FLOW CYTOMETRY FACILITY FOR THE PETER DOHERTY INSTITUTE

The establishment of a flow cytometry facility in the new Peter Doherty Institute for Infection and Immunity will enhance capacity to invest..

ARC CENTRE OF EXCELLENCE FOR ADVANCED MOLECULAR IMAGING

The Centre of Excellence in Advanced Molecular Imaging will innovatively integrate physics, chemistry and biology to unravel the complex mol..

Grants

Awarded by National Institute of Allergy and Infectious Diseases

Funding Acknowledgements

We thank L. Tan, M. Bhati, J. Waddington, B. O'Sullivan, M. Ciula and staff at the Australian synchrotron and the Monash macromolecular crystallization facility for technical assistance; P. Savage (Brigham Young University) for alpha-galactosylceramide; S.A. Porcelli (Albert Einstein College of Medicine) for the BK6 clone; and J. Altman for the design of CD1a protein expression constructs. Supported by NIAID (R01 AR048632 and AI049313 to D.B.M.), the National Health and Medical Research Council of Australia (1013667; Early Career Fellowship to D.G.P.; Senior Principal Research Fellowship 1020770 to D.I.G.; and NHMRC Australia Fellowship AF50 to J.R.), the Australian Research Council (CE140100011 and LE110100106; Future Fellowships to S.G. and A.P.U.) and the Dermatology Foundation (A.d.J.).