Journal article

CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens

Annemieke de Jong, Tan-Yun Cheng, Shouxiong Huang, Stephanie Gras, Richard W Birkinshaw, Anne G Kasmar, Ildiko Van Rhijn, Victor Pena-Cruz, Daniel T Ruan, John D Altman, Jamie Rossjohn, D Branch Moody

Nature Immunology | NATURE PUBLISHING GROUP | Published : 2014

Abstract

T cells autoreactive to the antigen-presenting molecule CD1a are common in human blood and skin, but the search for natural autoantigens has been confounded by background T cell responses to CD1 proteins and self lipids. After capturing CD1a-lipid complexes, we gently eluted ligands while preserving non-ligand-bound CD1a for testing lipids from tissues. CD1a released hundreds of ligands of two types. Inhibitory ligands were ubiquitous membrane lipids with polar head groups, whereas stimulatory compounds were apolar oils. We identified squalene and wax esters, which naturally accumulate in epidermis and sebum, as autoantigens presented by CD1a. The activation of T cells by skin oils suggested..

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Grants

Awarded by US National Institutes of Health


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Awarded by OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH


Funding Acknowledgements

We thank C. Higgins (Columbia University) for the photo of sebaceous glands; L.L. Tan for technical support for production of the BC2 TCR; and members of the US National Institutes of Health Tetramer Facility for the preparation of CD1a. Supported by the Burroughs Wellcome Fund (D.B.M.), the Mizutani Foundation, the US National Institutes of Health (AR R01048632 and AI 049313 to D.B.M.; K08AI089858 to A.G.K.; Tetramer Facility contract HHSN272201300006C to J.D.A.), the Dermatology Foundation (A.d.J.), the American Skin Association (A.d.J.), the Australian Research Council (S.G.) and the National Health and Medical Research Council of Australia (J.R.).