Journal article

alpha beta T cell antigen receptor recognition of CD1a presenting self lipid ligands

Richard W Birkinshaw, Daniel G Pellicci, Tan-Yun Cheng, Andrew N Keller, Maria Sandoval-Romero, Stephanie Gras, Annemieke de Jong, Adam P Uldrich, D Branch Moody, Dale I Godfrey, Jamie Rossjohn

NATURE IMMUNOLOGY | NATURE PUBLISHING GROUP | Published : 2015

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..

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Grants

Awarded by NIAID


Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Research Council


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN 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.).