title: NK Cells Respond to Haptens by the Activation of Calcium Permeable Plasma Membrane Channels.
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.
authors.affiliation: Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland.
authors.forename: Camille
authors.initials: C
authors.lastname: Grandclément
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Horst
authors.initials: H
authors.lastname: Pick
authors.affiliation: Laboratory of Physical Chemistry of Polymers and Membranes, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Horst
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland.
authors.forename: Werner
authors.initials: W
authors.lastname: Held
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling; D002460:Cell Line; D002463:Cell Membrane Permeability; D003877:Dermatitis, Contact / Q000276:immunology*; D000939:Epitopes; D057809:HEK293 Cells; D006241:Haptens / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000187:drug effects*; D008214:Lymphocytes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050052:TRPC Cation Channels / Q000378:metabolism / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D000939:Epitopes; D006241:Haptens; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel