Vstm3 is a member of the CD28 family and an important modulator of T-cell function

Steven D. Levin, David W. Taft, Cameron S. Brandt, Christoph Bucher, Edward D. Howard, Eric M. Chadwick, Janet Johnston, Angela Hammond, Kristen Bontadelli, Daniel Ardourel, Luann Hebb, Anitra Wolf, Thomas R. Bukowski, Mark W. Rixon, Joseph L. Kuijper, Craig D. Ostrander, James W. West, Janine Bilsborough, Brian Fox, Zeren GaoWenfeng Xu, Fred Ramsdell, Bruce R. Blazar, Katherine E. Lewis

Research output: Contribution to journalArticle

138 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)902-915
Number of pages14
JournalEuropean Journal of Immunology
Volume41
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Autoimmunity
  • Inhibitory receptors
  • Knockout mice
  • T cells

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    Levin, S. D., Taft, D. W., Brandt, C. S., Bucher, C., Howard, E. D., Chadwick, E. M., Johnston, J., Hammond, A., Bontadelli, K., Ardourel, D., Hebb, L., Wolf, A., Bukowski, T. R., Rixon, M. W., Kuijper, J. L., Ostrander, C. D., West, J. W., Bilsborough, J., Fox, B., ... Lewis, K. E. (2011). Vstm3 is a member of the CD28 family and an important modulator of T-cell function. European Journal of Immunology, 41(4), 902-915. https://doi.org/10.1002/eji.201041136