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PMID:19011627

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Citation

Yu, X, Harden, K, Gonzalez, LC, Francesco, M, Chiang, E, Irving, B, Tom, I, Ivelja, S, Refino, CJ, Clark, H, Eaton, D and Grogan, JL (2009) The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat. Immunol. 10:48-57

Abstract

Here we have identified a surface protein, TIGIT, containing an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif that was expressed on regulatory, memory and activated T cells. Poliovirus receptor, which is expressed on dendritic cells, bound TIGIT with high affinity. A TIGIT-Fc fusion protein inhibited T cell activation in vitro, and this was dependent on the presence of dendritic cells. The binding of poliovirus receptor to TIGIT on human dendritic cells enhanced the production of interleukin 10 and diminished the production of interleukin 12p40. Knockdown of TIGIT with small interfering RNA in human memory T cells did not affect T cell responses. TIGIT-Fc inhibited delayed-type hypersensitivity reactions in wild-type but not interleukin 10-deficient mice. Our data suggest that TIGIT exerts immunosuppressive effects by binding to poliovirus receptor and modulating cytokine production by dendritic cells.

Links

PubMed Online version:10.1038/ni.1674

Keywords

Amino Acid Sequence; Animals; CHO Cells; Cell Communication; Cell Differentiation; Cells, Cultured; Cricetinae; Cricetulus; Dendritic Cells/cytology; Dendritic Cells/immunology; Dendritic Cells/metabolism; Down-Regulation; Humans; Immune Tolerance; Immunologic Memory; Interleukin-10/biosynthesis; Interleukin-12 Subunit p40/metabolism; Membrane Proteins/chemistry; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Protein Binding; Receptors, Immunologic/chemistry; Receptors, Immunologic/genetics; Receptors, Immunologic/metabolism; Receptors, Virus/genetics; Receptors, Virus/metabolism; Sequence Alignment; T-Lymphocytes/immunology; T-Lymphocytes/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PVR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q495A1

F

Seeded From UniProt

complete

MOUSE:TIGIT

involved_in

GO:0032733: positive regulation of interleukin-10 production

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q495A1

P

Seeded From UniProt

complete

MOUSE:TIGIT

involved_in

GO:0032695: negative regulation of interleukin-12 production

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q495A1

P

Seeded From UniProt

complete

MOUSE:TIGIT

located_in

GO:0009986: cell surface

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q495A1

C

Seeded From UniProt

complete

MOUSE:TIGIT

involved_in

GO:0050868: negative regulation of T cell activation

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q495A1

P

Seeded From UniProt

complete

HUMAN:TIGIT

located_in

GO:0009986: cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TIGIT

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15151

F

Seeded From UniProt

complete

HUMAN:TIGIT

acts_upstream_of_or_within

GO:0050868: negative regulation of T cell activation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TIGIT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92692

F

Seeded From UniProt

complete

HUMAN:TIGIT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15151

F

Seeded From UniProt

complete

HUMAN:TIGIT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NQS3

F

Seeded From UniProt

complete

HUMAN:TIGIT

involved_in

GO:0032733: positive regulation of interleukin-10 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TIGIT

involved_in

GO:0032695: negative regulation of interleukin-12 production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TIGIT

involved_in

GO:0050868: negative regulation of T cell activation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NECT2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q495A1

F

Seeded From UniProt

complete

HUMAN:NECT3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q495A1

F

Seeded From UniProt

complete


See also

References

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