TY  - JOUR
A1  - Herrmann, Thomas
A1  - Karunakaran, Mohindar M.
T1  - Butyrophilins: γδ T cell receptor ligands, immunomodulators and more
JF  - Frontiers in Immunology
N2  - Butyrophilins (BTN) are relatives of the B7 family (e.g., CD80, PD-L1). They fulfill a wide range of functions including immunomodulation and bind to various receptors such as the γδ T cell receptor (γδTCR) and small molecules. One intensively studied molecule is BTN3A1, which binds via its cytoplasmic B30.2 domain, metabolites of isoprenoid synthesis, designated as phosphoantigen (PAg), The enrichment of PAgs in tumors or infected cells is sensed by Vγ9Vδ2 T cells, leading to the proliferation and execution of effector functions to remove these cells. This article discusses the contribution of BTNs, the related BTNL molecules and SKINT1 to the development, activation, and homeostasis of γδ T cells and their immunomodulatory potential, which makes them interesting targets for therapeutic intervention.
KW  - butyrophilin
KW  - immune therapy
KW  - T cell receptor
KW  - γδ T cell
KW  - BTN3A1
KW  - BTN2A1
KW  - phosphoantigen
KW  - tumor
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265944
SN  - 1664-3224
VL  - 13
ER  - 
TY  - JOUR
A1  - Herrmann, Thomas
A1  - Karunakaran, Mohindar M.
T1  - The Vγ9Vδ2 T cell antigen receptor and butyrophilin-3 A1: models of interaction, the possibility of co-evolution, and the case of dendritic epidermal T cells
N2  - Most circulating human gamma delta T cells are Vγ9Vδ2 T  cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains show a Vγ9-JP (Vγ2-Jγ1.2) rearrangement and are paired with Vδ2-containing δ-chains, a dominantTCR configuration, which until recently seemed to occur in primates only. Vγ9Vδ2 T cells respond to phosphoantigens (PAg) such as (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is produced by many pathogens and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. A prerequisite for PAg-induced activation is the contact of Vγ9Vδ2 T cells with cells expressing butyrophilin-3 A1 (BTN3A1). We will first critically review models of how BTN3 might act in PAg-mediated Vγ9Vδ2 T cell activation and then address putative co-evolution of Vγ9, Vδ2, and BTN3 genes. In those rodent and lagomorphs used as animal models, all three genes are lost but a data-base analysis showed that they emerged together with placental mammals. A strong concomitant conservation of functional Vγ9, Vδ2, and BTN3 genes in other species suggests co-evolution of these three genes. A detailed analysis was performed for the new world camelid alpaca (Vicugna pacos). It provides an excellent candidate for a non-primate species with presumably functional Vγ9Vδ2 T cells since TCR rearrangements share features characteristic for PAg-reactive primate Vγ9Vδ2 TCR and proposed PAg-binding sites of BTN3A1 have been conserved. Finally, we analyze the possible functional relationship between the butyrophilin-family member Skint1 and the γδTCR-V genes used by murine dendritic epithelialT cells (DETC). Among placental mammals, we identify five rodents, the cow, a bat, and the cape golden mole as the only species concomitantly possessing potentially functional homologs of murineVγ3,Vδ4 genes, and Skint1 gene and suggest to search for DETC like cells in these species.
KW  - γδ T cells
KW  - Vγ9Vδ2 T cell
KW  - phosphoantigen
KW  - BTN3
KW  - alpaca
KW  - co-evolution
KW  - DETC
KW  - Skint1
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111141
ER  -