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

• Published in: Immunity (Cambridge, Mass.) Mass.), 2012-09, Vol.37 (3), p.524-534
• Main Authors: Zeng, Xun, Wei, Yu-Ling, Huang, Jun, Newell, Evan W., Yu, Hongxiang, Kidd, Brian A., Kuhns, Michael S., Waters, Ray W., Davis, Mark M., Weaver, Casey T., Chien, Yueh-hsiu
• Format: Article
• Language: English
• Subjects: Algal Proteins - immunology; Algal Proteins - metabolism; Amino Acid Sequence; Animals; Antigens - immunology; Antigens - metabolism; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Base Sequence; Binding Sites - genetics; Cells, Cultured; Female; Flow Cytometry; Humans; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukin-17 - metabolism; Kinetics; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Transgenic; Phycoerythrin - immunology; Phycoerythrin - metabolism; Protein Binding - immunology; Receptors, Antigen, T-Cell, gamma-delta - genetics; Receptors, Antigen, T-Cell, gamma-delta - immunology; Receptors, Antigen, T-Cell, gamma-delta - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.06.011

γδ T cells contribute uniquely to immune competence. Nevertheless, how they function remains an enigma. It is unclear what most γδ T cells recognize, what is required for them to mount an immune response, and how the γδ 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 γδ T cell antigen. Employing this specificity, we demonstrated that antigen recognition activated naive γδ T cells to make interleukin-17 and respond to cytokine signals that perpetuate the response. High frequencies of antigen-specific γδ T cells in naive animals and their ability to mount effector response without extensive clonal expansion allow γδ 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. ► Murine and human γδ T cells recognize a microbial encoded B cell antigen ► Naive γδ T cells develop into IL-17 effectors in response to this antigen ► Antigen-activated γδ T cells gain the ability to respond to cytokine signals ► Robust and sustained IL-17 production requires both TCR and cytokine signals