Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.00828
Keywords
human gamma delta T cell; T cell receptor; antigenic activation; phosphoantigens; butyrophilin; B30.2
Categories
Funding
- INSERM
- CNRS
- Universite de Nantes
- Institut National du Cancer (INCa, PLBio)
- Agence Nationale de la Recherche (ANR, GDSTRESS)
- Ligue Nationale contre le Cancer (AO InterRegional)
- Fondation pour la Recherche Medicale (FRM Equipe)
- Canceropole Grand-Ouest
- SANOFI
- National Research Agency Investissements d'Avenir [ANR-11-LABX-0016-01, ANR-10-IBHU-005]
- Nantes Metropole
- Region Pays de la Loire
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V gamma 9V delta 2 T cells represent a major unconventional gamma delta T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of V gamma 9V delta 2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by V gamma 9V delta 2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique gamma delta T cell subset.
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