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Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes

2016; Rockefeller University Press; Volume: 213; Issue: 2 Linguagem: Inglês

10.1084/jem.20150435

1540-9538

Kerstin Sarter, Elisa Leimgruber, Florian Gobet, Vishal Agrawal, Isabelle Dunand-Sauthier, Emmanuèle Barras, Béatris Mastelic-Gavillet, Arun T. Kamath, Paola Fontannaz, Leslie Guéry, Fernanda do Valle Durães, Carla Lippens, Ulla Ravn, Marie‐Laure Santiago‐Raber, Giovanni Magistrelli, Nicolas Fischer, Claire‐Anne Siegrist, Stéphanie Hugues, Walter Reith,

Immune Cell Function and Interaction

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.