Research ArticleSKIN INFLAMMATION

Human T cell response to CD1a and contact dermatitis allergens in botanical extracts and commercial skin care products

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Science Immunology  03 Jan 2020:
Vol. 5, Issue 43, eaax5430
DOI: 10.1126/sciimmunol.aax5430

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Oily skin allergens hole up inside CD1a

Contact dermatitis induced by allergens in personal care products is a common cause of skin rashes, but the molecular mechanisms leading to T cell activation are poorly understood. Nicolai et al. tested known contact allergens for their ability to boost IFN-γ production by human T cells autoreactive to the CD1a antigen presentation molecule. Several hydrophobic chemicals came up as “hits,” including farnesol, a compound often used as a fragrance. Structural analysis of CD1a-farnesol complexes revealed that farnesol is buried deep within CD1a’s antigen-binding cleft beyond the reach of T cell receptor chains. These findings suggest that several hydrophobic contact allergens elicit T cell–mediated hypersensitivity reactions through displacement of self-lipids normally bound to CD1a, thereby exposing T cell–stimulatory surface regions of CD1a that are normally hidden.

Abstract

During industrialization, humans have been exposed to increasing numbers of foreign chemicals. Failure of the immune system to tolerate drugs, cosmetics, and other skin products causes allergic contact dermatitis, a T cell–mediated disease with rising prevalence. Models of αβ T cell response emphasize T cell receptor (TCR) contact with peptide-MHC complexes, but this model cannot readily explain activation by most contact dermatitis allergens, which are nonpeptidic molecules. We tested whether CD1a, an abundant MHC I–like protein in human skin, mediates contact allergen recognition. Using CD1a-autoreactive human αβ T cell clones to screen clinically important allergens present in skin patch testing kits, we identified responses to balsam of Peru, a tree oil widely used in cosmetics and toothpaste. Additional purification identified benzyl benzoate and benzyl cinnamate as antigenic compounds within balsam of Peru. Screening of structurally related compounds revealed additional stimulants of CD1a-restricted T cells, including farnesol and coenzyme Q2. Certain general chemical features controlled response: small size, extreme hydrophobicity, and chemical constraint from rings and unsaturations. Unlike lipid antigens that protrude to form epitopes and contact TCRs, the small size of farnesol allows sequestration deeply within CD1a, where it displaces self-lipids and unmasks the CD1a surface. These studies identify molecular connections between CD1a and hypersensitivity to consumer products, defining a mechanism that could plausibly explain the many known T cell responses to oily substances.

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