Abstract
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.
© 2016 Sarter et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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Butyrophilins
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cancer Vaccines / immunology
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Cell Line
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Gene Expression Regulation
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Genes, MHC Class II*
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Humans
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Immunity, Cellular
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nuclear Proteins / genetics
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Nuclear Proteins / immunology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Regulatory Factor X Transcription Factors
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Trans-Activators / genetics
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Trans-Activators / immunology
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Transcription Factors / genetics
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Transcription Factors / immunology
Substances
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BTN2A2 protein, human
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Butyrophilins
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Cancer Vaccines
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DNA-Binding Proteins
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MHC class II transactivator protein
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Membrane Glycoproteins
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Nuclear Proteins
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RNA, Messenger
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Regulatory Factor X Transcription Factors
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Trans-Activators
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Transcription Factors