Abstract
The ability to recognize small organic molecules and chemical modifications of host molecules is an essential capability of the adaptive immune system, which until now was thought to be mediated mainly by B cell antigen receptors. Here we report that small molecules, such as cyanine 3 (Cy3), a synthetic fluorescent molecule, and 4-hydroxy-3-nitrophenylacetyl (NP), one of the most noted haptens, are γδ T cell antigens, recognized directly by specific γδ TCRs. Immunization with Cy3 conjugates induces a rapid Cy3-specific γδ T cell IL-17 response. These results expand the role of small molecules and chemical modifications in immunity and underscore the role of γδ T cells as unique adaptive immune cells that couple B cell-like antigen recognition capability with T cell effector function.