Major Histocompatibility Complex class II; molecular immunology; T cell immunology; negative costimulatory molecules; adaptive immunity; butyrophylin proteins; BTN2A2; antigen presenting cells; knockout and transgenic mouse models; checkpoint regulators
Rhodes DA, ReithWalter (2017), Butyrophilin (BTN) family interactions
, 60, Reactome Pathway Knowledgebase, USA 60.
Lippens Carla, Duraes Fernanda V., Dubrot Juan, Brighouse Dale, Lacroix Mathilde, Irla Magali, Aubry-Lachainaye Jean-Pierre, Reith Walter, Mandl Judith N., Hugues Stéphanie (2016), IDO-orchestrated crosstalk between pDCs and Tregs inhibits autoimmunity, in Journal of Autoimmunity
, 75, 39-49.
Kiyeko Gaëlle Wambiekele, Hatterer Eric, Herren Suzanne, Di Ceglie Irene, van Lent Peter L., Reith Walter, Kosco-Vilbois Marie, Ferlin Walter, Shang Limin (2016), Spatiotemporal expression of endogenous TLR4 ligands leads to inflammation and bone erosion in mouse collagen-induced arthritis, in European Journal of Immunology
, 46(11), 2629-2638.
Eren Remzi Onur, Reverte Marta, Rossi Matteo, Hartley Mary-Anne, Castiglioni Patrik, Prevel Florence, Martin Ricardo, Desponds Chantal, Lye Lon-Fye, Drexler Stefan K., Reith Walter, Beverley Stephen M., Ronet Catherine, Fasel Nicolas (2016), Mammalian Innate Immune Response to a Leishmania -Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence, in Cell Host & Microbe
, 20(3), 318-328.
Rhodes David A., Reith Walter, Trowsdale John (2016), Regulation of Immunity by Butyrophilins, in Annual Review of Immunology
, 34(1), 151-172.
PicardCapucine, ReithWalter (2016), Major Histocompatibility Complex Class II Deficiency, in Ratcliffe Michael (ed.), Academic Press, United States of America, 378-390.
Rota Giorgia, Ludigs Kristina, Siegert Stefanie, Tardivel Aubry, Morgado Leonor, Reith Walter, De Gassart Aude, Guarda Greta (2016), T Cell Priming by Activated Nlrc5-Deficient Dendritic Cells Is Unaffected despite Partially Reduced MHC Class I Levels., in Journal of immunology (Baltimore, Md. : 1950)
, 196(7), 2939-46.
Sarter Kerstin, Leimgruber Elisa, Gobet Florian, Agrawal Vishal, Dunand-Sauthier Isabelle, Barras Emmanuèle, Mastelic-Gavillet Béatris, Kamath Arun, Fontannaz Paola, Guéry Leslie, Duraes Fernanda do Valle, Lippens Carla, Ravn Ulla, Santiago-Raber Marie-Laure, Magistrelli Giovanni, Fischer Nicolas, Siegrist Claire-Anne, Hugues Stéphanie, Reith Walter (2016), Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes., in The Journal of experimental medicine
, 213(2), 177-87.
de la SalleHenri, ReithWalter, Bare Lymphocyte Syndrome, Type I, Springer, USA.
ReithWakter, Bare Lymphocyte Syndrome, Type II, Springer, USA.
Butyrophilins are cell-surface glycoproteins related to the B7 family of co-stimulatory molecules implicated in the regulation of T-cell responses. There is growing evidence that butyrophilins play diverse roles in the immune system. Our work on the regulation of MHC class II (MHCII) expression revealed that the gene encoding butyrophilin 2A2 (BTN2A2) is a target of the MHCII-specific transcription machinery. Human BTN2A2 and mouse Btn2a2 genes are regulated in antigen presenting cells (APCs), thymic epithelial cells (TECs) and IFN?-induced cells by regulatory factor X (RFX) and the class II transactivator (CIITA), two transcription factors dedicated for transcription of MHCII genes. The generation and analysis of Btn2a2-/- mice allowed us to provide conclusive genetic evidence that BTN2A2 functions as a co-inhibitory molecule that modulates T cell responses in vivo. The overall objectives of this project are to define the expression patterns, immunoregulatory functions and mechanisms of action of BTN2A2. Work will have 5 specific aims. Aim 1 is to characterize in detail the pattern of BTN2A2 expression in vivo under steady-state conditions in naïve mice, and during the course of adaptive immune responses. Aim 2 is to define in vivo functions of BTN2A2 by studying its role in TECs and thymocyte selection, and in shaping adaptive immune responses in the context of immunization, autoimmune diseases and tumor models. Aim 3 is to study conservation of the expression and function of BTN2A2 in humans. BTN2A2 expression by human tumors will also be assessed as it could, by analogy to other T cell inhibitory pathways, be implicated in escape from tumor immunosurveillance. Aim 4 is to identify the receptor(s) for BTN2A2 on T cells by three strategies, analysis of suspected candidates, using a novel ligand-based receptor-capture assay, and performing expression-cloning screens. Aim 5 is to characterize the “interactome” of BTN2A2, and its interaction partners in APCs, by using both affinity-purification and proximity labeling with biotin (BioID). These investigations are anticipated to fill major gaps in our knowledge on butyrophilin biology. They will in particular provide detailed insights on a new T cell co-inhibitory axis that could be of potential therapeutic relevance for the treatment of cancer or autoimmune diseases.