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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation
  • Antigens, CD1 / genetics
  • Antigens, CD1 / immunology*
  • Autoantigens / chemistry
  • Autoantigens / immunology*
  • Autoantigens / isolation & purification
  • HEK293 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Lipids / chemistry
  • Lipids / immunology*
  • Lipids / isolation & purification
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Protein Binding
  • Recombinant Proteins / genetics
  • Skin / immunology*
  • Structure-Activity Relationship
  • T-Lymphocytes / immunology*


  • Antigens, CD1
  • Autoantigens
  • CD1a antigen
  • Lipids
  • Recombinant Proteins

Associated data

  • GENBANK/KF751594
  • GENBANK/KF751595
  • GENBANK/KF751596
  • GENBANK/KF751597