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

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

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92 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)177 - 185
Number of pages9
JournalNature Immunology
Volume15
Issue number2
DOIs
Publication statusPublished - 2014

Cite this

de Jong, A., Cheng, T-Y., Huang, S., Gras, S., Birkinshaw, R. W., Kasmar, A., Van Rhijn, I., Pena-Cruz, V., Ruan, D., Altman, J. D., Rossjohn, J., & Moody, D. B. (2014). CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens. Nature Immunology, 15(2), 177 - 185. https://doi.org/10.1038/ni.2790