The Phylogenomic Approach Suggests That Butyrophilins Have Ligands Beyond Gamma–Delta Receptors

Since γδ T cells are present in all jawed vertebrates, we wondered whether butyrophilins, proteins that play a key role in the activation of these cells, were also present in these organisms. Our analyses revealed the presence of genes encoding butyrophilins across all jawed vertebrates, including in squamates, a reptilian clade that is nonetheless reported in the literature to have lost γδ T cells. The conservation of butyrophilins in this group, despite the absence of their only known cellular partner, suggests that they may fulfill an alternative function, possibly through interaction with another ligand. Given their strong conservation across jawed vertebrates, it is reasonable to hypothesize that this alternative ligand may also be present in humans.