title: Vstm3 is a member of the CD28 family and an important modulator of T-cell function.
abstract: Members of the CD28 family play important roles in regulating T-cell functions and share a common gene structure profile. We have identified VSTM3 as a protein whose gene structure matches that of the other CD28 family members. This protein (also known as TIGIT and WUCAM) has been previously shown to affect immune responses and is expressed on NK cells, activated and memory T cells, and Tregs. The nectin-family proteins CD155 and CD112 serve as counter-structures for VSTM3, and CD155 and CD112 also bind to the activating receptor CD226 on T cells and NK cells. Hence, this group of interacting proteins forms a network of molecules similar to the well-characterized CD28-CTLA-4-CD80-CD86 network. In the same way that soluble CTLA-4 can be used to block T-cell responses, we show that soluble Vstm3 attenuates T-cell responses in vitro and in vivo. Moreover, animals deficient in Vstm3 are more sensitive to autoimmune challenges indicating that this new member of the CD28 family is an important regulator of T-cell responses.
authors.affiliation: Department of Immunology, ZymoGenetics, Inc., Seattle, WA, USA. svlv@novonordisk.com
authors.forename: Steven D
authors.initials: SD
authors.lastname: Levin
authors.forename: David W
authors.initials: DW
authors.lastname: Taft
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Brandt
authors.forename: Christoph
authors.initials: C
authors.lastname: Bucher
authors.forename: Edward D
authors.initials: ED
authors.lastname: Howard
authors.forename: Eric M
authors.initials: EM
authors.lastname: Chadwick
authors.forename: Janet
authors.initials: J
authors.lastname: Johnston
authors.forename: Angela
authors.initials: A
authors.lastname: Hammond
authors.forename: Kristen
authors.initials: K
authors.lastname: Bontadelli
authors.forename: Daniel
authors.initials: D
authors.lastname: Ardourel
authors.forename: LuAnn
authors.initials: L
authors.lastname: Hebb
authors.forename: Anitra
authors.initials: A
authors.lastname: Wolf
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bukowski
authors.forename: Mark W
authors.initials: MW
authors.lastname: Rixon
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuijper
authors.forename: Craig D
authors.initials: CD
authors.lastname: Ostrander
authors.forename: James W
authors.initials: JW
authors.lastname: West
authors.forename: Janine
authors.initials: J
authors.lastname: Bilsborough
authors.forename: Brian
authors.initials: B
authors.lastname: Fox
authors.forename: Zeren
authors.initials: Z
authors.lastname: Gao
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xu
authors.forename: Fred
authors.initials: F
authors.lastname: Ramsdell
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D051379:Mice; D051381:Rats; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D011971:Receptors, Immunologic; C556305:T cell Ig and ITIM domain protein, mouse; C534712:TIGIT protein, human; C558389:TIGIT protein, rat