Macrophages express multiple ligands for γδ TCRs

As only a handful of ligands have been identified, the general nature of the ligands recognized by γδ T cells remains unresolved. In this study, soluble multimerized γδ T cell receptors (smTCRs) representing the TCRs of two γδ T cell subsets common in the mouse were used to detect and track their own ligands. Ligands for both subsets were found on resident peritoneal macrophages taken from untreated mice, and the expression of both was further induced by Listeria monocytogenes infection. Nevertheless, the two types of ligand differ from one another in abundance, in the kinetics of their induction following Listeria infection, and in their ability to be induced by in vitro culture with lipopolysaccharide (LPS). Surprisingly, because both are detectable on normal macrophages, these host-derived ligands are likely expressed constitutively, but are induced to higher levels of expression by stress or inflammation. In contrast to T22 and other known cell surface ligands for γδ T cells in mice and humans, expression of these smTCR-defined ligands does not depend on β2-microglobulin, suggesting that they are not MHC class I or class I-like molecules.