title: CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens.
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.
authors.affiliation: 1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2] [3].
authors.forename: Annemieke
authors.initials: A
authors.lastname: de Jong
authors.affiliation: 1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. [2].
authors.forename: Tan-Yun
authors.initials: TY
authors.lastname: Cheng
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Shouxiong
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Australia.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Birkinshaw
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Kasmar
authors.affiliation: 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.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
authors.affiliation: Infectious Disease Department, Boston University, Boston, Massachusetts, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Peña-Cruz
authors.affiliation: Department of Gastrointestinal and General Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Ruan
authors.affiliation: Emory Vaccine Center, Atlanta, Georgia, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.affiliation: 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.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics; D012867:Skin / Q000276:immunology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D001324:Autoantigens; C419393:CD1a antigen; D008055:Lipids; D011994:Recombinant Proteins