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

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.

Hypersensitivities following allergen antigen recognition by unconventional T cells

“…This included farnesol, related to farnesyl pyrophosphate, the biosynthetic precursor of the human skin oil squalene. Farnesol was able to stimulate polyclonal T cells in vitro when presented by CD1a in some donors 55 . Structural analysis revealed farnesol occupied only 36% of the CD1a cleft (Figure 3A) and was likely protected entirely from TCR surveillance 55 .…”

The Global Rise and the Complexity of Sesame Allergy: Prime Time to Regulate Sesame in the United States of America?

“…Lipid allergens in general are small hydrophobic chemicals present in plant oils (sesame oil, cashew nutshell oil, poison ivy, poison oak, poison sumac) and cosmetics such as fragrance, toothpaste, and hair dyes (e.g., balsam of Peru, urushiol of poison ivy, farnesol, benzyl benzoate, benzyl cinnamate) [86][87][88][89][90][91]. The mechanisms through which they trigger allergic reactions have been deciphered for some of the lipid allergens, but not for sesame lipid allergens [86][87][88][89][90][91]. Furthermore, some of these lipid allergens show structures similar to that of sesame lipid allergens.…”

“…Entry of lipid allergens into the body of susceptible subjects leads to their uptake by the APCs, such as Langerhans cells and presentation to specific naïve T cells to initiate their proliferation and differentiation into effector and memory T cells [86][87][88][89][90][91] (Figure 3). There are two models to explain specifics on how APCs are able to do this.…”

“…The first model suggests that lipid allergens, which are considered as haptens because of their very small sizes of <500 Daltons, form covalent bonds to host proteins, resulting in an immunogenic hapten-carrier complex molecule that is then presented by the APCs in the context of MHC class II molecules to T cells that get activated [86]. The second, and most recent, model suggests that lipids allergens can also directly bind to CD1a molecule, a non-classical MHC molecule expressed by the Langerhans cells (a type of APC) in the skin, by displaying the self-lipids normally bound to the CD1a inside its molecular cleft or hole [87][88][89][90][91]. This results in the presentation of lipid allergens to which T cell reactions are initiated, resulting in the formation of specific effector and memory T cells.…”

“…Re-exposure of a previously sensitized subject to the same lipid allergens results in their entry and presentation of by the APCs to the pre-formed allergen specific effector and memory T cells [86][87][88][89][90][91] (Figure 3). This results in their activation, proliferation, and release of cytokines and chemokines into the local tissues and eventually into the blood.…”