γδ T Cells Recognize a Microbial Encoded B Cell Antigen to Initiate a Rapid Antigen-Specific Interleukin-17 Response

gamma delta T cells contribute uniquely to immune competence. Nevertheless, how they function remains an enigma. It is unclear what most gamma delta T cells recognize, what is required for them to mount an immune response, and how the gamma delta T cell response is integrated into host immune defense. Here, we report that a noted B cell antigen, the algae protein phycoerythrin (PE), is a murine and human gamma delta T cell antigen. Employing this specificity, we demonstrated that antigen recognition activated naive gamma delta T cells to make interleukin-17 and respond to cytokine signals that perpetuate the response. High frequencies of antigen-specific gamma delta T cells in naive animals and their ability to mount effector response without extensive clonal expansion allow gamma delta T cells to initiate a swift, substantial response. These results underscore the adaptability of lymphocyte antigen receptors and suggest an antigen-driven rapid response in protective immunity prior to the maturation of classical adaptive immunity.