title: B7-H5 costimulates human T cells via CD28H.
abstract: The B7/CD28 family has profound modulatory effects in immune responses and constitutes an important target for the development of novel therapeutic drugs against human diseases. Here we describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. After extensive screening in a receptor array, a B7-like molecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 is constitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via an AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathway regulating human T-cell responses.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Zhu
authors.forename: Sheng
authors.initials: S
authors.lastname: Yao
authors.forename: Bettina P
authors.initials: BP
authors.lastname: Iliopoulou
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Mathew M
authors.initials: MM
authors.lastname: Augustine
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Phennicie
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Flies
authors.forename: Megan
authors.initials: M
authors.lastname: Broadwater
authors.forename: William
authors.initials: W
authors.lastname: Ruff
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
authors.forename: Linghua
authors.initials: L
authors.lastname: Zheng
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.forename: Gefeng
authors.initials: G
authors.lastname: Zhu
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060887:B7 Antigens; D018106:CD28 Antigens / Q000737:chemistry / Q000378:metabolism*; D018920:Coculture Techniques; D000939:Epitopes / Q000276:immunology; D005452:Fluoresceins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015894:Genome, Human / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D013388:Succinimides / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D060887:B7 Antigens; D018106:CD28 Antigens; D000939:Epitopes; D005452:Fluoresceins; D008024:Ligands; D008565:Membrane Proteins; D013388:Succinimides; C585279:TMIGD2 protein, human; C000588758:VSIR protein, human; C076715:pervanadate; D019000:Phosphotyrosine; D014638:Vanadates