Abstract
Natural Killer (NK) cells mediate innate immunity to infected and transformed cells. Yet, NK cells can also mount hapten-specific recall responses thereby contributing to contact hypersensitivity (CHS). However, since NK cells lack antigen receptors that are used by the adaptive immune system to recognize haptens, it is not clear if NK cells respond directly to haptens and, if so, what mediates these responses. Here we show that among four haptens the two that are known to induce NK cell-dependent CHS trigger the rapid influx of extracellular Ca2+ into NK cells and lymphocyte cell lines. Thus lymphocytes can respond to haptens independent of antigen presentation and antigen receptors. We identify the Ca2+-permeable cation channel TRPC3 as a component of the lymphocyte response to one of these haptens. These data suggest that the response to the second hapten is based on a distinct mechanism, consistent with the capacity of NK cells to discriminate haptens. These findings raise the possibility that antigen-receptor independent activation of immune cells contributes to CHS.
Highlights
Haptens are small molecules that can elicit an immune response only when attached to larger carrier molecules such as proteins
The induction of contact hypersensitivity (CHS) depends on antigen presentation and the discriminatory capacity of antigen-receptors expressed by T cells together with the capacity of the adaptive immune system to form hapten-specific memory
Natural Killer (NK) cells can respond to odorants and haptens in the absence of antigen presentation We initially hypothesized that olfactory receptors (ORs), which are expressed in the olfactory epithelium where they detect volatile substances that are structurally similar to haptens (S1 Fig) mediate hapten recognition by NK cells
Summary
Haptens are small molecules that can elicit an immune response only when attached to larger carrier molecules such as proteins. Subsequent re-exposure to the same hapten applied to a different skin area of the animal can result in strong a strong inflammatory reaction or contact hypersensitivity (CHS). Hapten-induced CHS represents the prevalent animal model of allergic contact dermatitis (ACD), a delayed hypersensitivity reaction that is one of the most prevalent skin diseases in the world [1]. The induction of CHS depends on antigen presentation and the discriminatory capacity of antigen-receptors expressed by T cells together with the capacity of the adaptive immune system to form hapten-specific memory. Antigen-specific immune recognition is mediated by receptors that are assembled randomly using RAG-dependent somatic recombination and that are clonally expressed on T cells. This receptor system can recognize virtually any molecular
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