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

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

Nature immunology (2013-12-24)
Annemieke de Jong, Tan-Yun Cheng, Shouxiong Huang, Stephanie Gras, Richard W Birkinshaw, Anne G Kasmar, Ildiko Van Rhijn, Victor Peña-Cruz, Daniel T Ruan, John D Altman, Jamie Rossjohn, D Branch Moody
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methyl palmitoleate, ≥99% (capillary GC), liquid
Sigma-Aldrich
Glyceryl trioleate, ≥99%
Sigma-Aldrich
Palmitoleic acid, ≥98.5% (GC), liquid
Sigma-Aldrich
Cholesterol, Sigma Grade, ≥99%
Sigma-Aldrich
Glyceryl tripalmitoleate, ≥98%, liquid
Sigma-Aldrich
Palmitoleyl alcohol, ≥98% (capillary GC)
Sigma-Aldrich
Cholesteryl palmitate, ≥98% (HPLC; detection at 205 nm)
Sigma-Aldrich
Squalene, ≥98%, liquid
Sigma-Aldrich
Monosialoganglioside GM3 from canine blood, ≥98%, lyophilized powder