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Nat Immunol. 2014 Feb;15(2):177-85. doi: 10.1038/ni.2790. Epub 2013 Dec 22.

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

Author information

1
1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] [3].
2
1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2].
3
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia.
5
1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
6
Infectious Disease Department, Boston University, Boston, Massachusetts, USA.
7
Department of Gastrointestinal and General Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
8
Emory Vaccine Center, Atlanta, Georgia, USA.
9
1] Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia. [2] Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff, UK.

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 that headless mini-antigens nest within CD1a and displace non-antigenic resident lipids with large head groups. Oily autoantigens naturally coat the surface of the skin; thus, this points to a previously unknown mechanism of barrier immunity.

PMID:
24362891
PMCID:
PMC3932764
DOI:
10.1038/ni.2790
[Indexed for MEDLINE]
Free PMC Article

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