Evidence has recently emerged that butyrophilins, which are members of the extended B7 family of co-stimulatory molecules, have diverse functions in the immune system. We found that the human and mouse genes encoding butyrophilin-2A2 (BTN2A2) are regulated by the class II trans-activator and regulatory factor X, two transcription factors dedicated to major histocompatibility complex class II expression, suggesting a role in T cell immunity. To address this, we generated Btn2a2-deficient mice. Btn2a2−/− mice exhibited enhanced effector CD4+ and CD8+ T cell responses, impaired CD4+ regulatory T cell induction, potentiated antitumor responses, and exacerbated experimental autoimmune encephalomyelitis. Altered immune responses were attributed to Btn2a2 deficiency in antigen-presenting cells rather than T cells or nonhematopoietic cells. These results provide the first genetic evidence that BTN2A2 is a co-inhibitory molecule that modulates T cell–mediated immunity.
Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes
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Kerstin Sarter, Elisa Leimgruber, Florian Gobet, Vishal Agrawal, Isabelle Dunand-Sauthier, Emmanuèle Barras, Béatris Mastelic-Gavillet, Arun Kamath, Paola Fontannaz, Leslie Guéry, Fernanda do Valle Duraes, Carla Lippens, Ulla Ravn, Marie-Laure Santiago-Raber, Giovanni Magistrelli, Nicolas Fischer, Claire-Anne Siegrist, Stéphanie Hugues, Walter Reith; Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes. J Exp Med 8 February 2016; 213 (2): 177–187. doi: https://doi.org/10.1084/jem.20150435
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