Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 4, Pages 902-915Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201041136
Keywords
Autoimmunity; Inhibitory receptors; Knockout mice; T cells
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Funding
- NCI NIH HHS [P01 CA142106] Funding Source: Medline
- NHLBI NIH HHS [R01 HL056067] Funding Source: Medline
- NIAID NIH HHS [P01 AI056299, R01 AI034495] Funding Source: Medline
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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 familymembers. 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.
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