B7-H4, a molecule of the B7 family, negatively regulates T cell immunity.
We identify a B7 family molecule, B7-H4, by protein sequence analysis and comparative molecular modeling. While B7-H4 mRNA is widely distributed in mouse and human peripheral tissues, cell surface expression of B7-H4 protein is limited and shows an inducible pattern on hematopoietic cells. Putative receptor of B7-H4 can be upregulated on activated T cells. By arresting cell cycle, B7-H4 ligation of T cells has a profound inhibitory effect on the growth, cytokine secretion, and development of cytotoxicity. Administration of B7-H4Ig into mice impairs antigen-specific T cell responses whereas blockade of endogenous B7-H4 by specific monoclonal antibody promotes T cell responses. B7-H4 thus may participate in negative regulation of cell-mediated immunity in peripheral tissues.
Sica
Gabriel L
GL
Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, MN 55905, USA.
Choi
In Hak
IH
Zhu
Gefeng
G
Tamada
Koji
K
Wang
Sheng Dian
SD
Tamura
Hideto
H
Chapoval
Andrei I
AI
Flies
Dallas B
DB
Bajorath
Jürgen
J
Chen
Lieping
L
D000595:Amino Acid Sequence; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015152:Blotting, Northern; D002453:Cell Cycle / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D018122:B7-1 Antigen; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; C475824:Vtcn1 protein, mouse