Immune recognition of phosphoantigen‐butyrophilin molecular complexes by γδ T cells

Abstract

The three main classes of lymphocytes bearing rearranged antigen receptors are B cells, αβ T cells, and γδ T cells. In humans, γδ T cells represent about 1 to 10% of circulating PBMCs 1,2 and are named as such because their antigen receptors are a product of recombination-activating gene (RAG)-mediated somatic gene rearrangement of variable (V), diversity (D), and joining (J) gene segments that are derived from the gamma and delta T cell receptor (TCR) gene loci. Akin to αβTCR gene rearrangement during αβ T cell development, the resulting rearranged gamma and delta chains heterodimerize

γδ T Cell in Cerebral Ischemic Stroke: Characteristic, Immunity-Inflammatory Role, and Therapy

“…Besides, in the fields of anti-bacterial immunity and tumor immunity, γδ T cells can be activated by phosphoantigens (pAgs), which includes (E)-1-hydroxy-2-methyl-but-2enyl pyrophosphate (HMBPP), dimethylallyl pyrophosphate (DMAPP) and isopentyl pyrophosphate (IPP), through γδ TCR ( 56 , 57 ). And butyrophilins (BTN)/butyrophilin-like molecules (BTNL) are core mediators of pAg sensing by γδ T cells ( 58 ). What's more, little research has focused on the signaling pathways that exist in γδ T cells intracellularly after activation through ligands combined with their receptors.…”

The Mysterious Actor—γδ T Lymphocytes in Chronic Lymphocytic Leukaemia (CLL)

“…However, the mevalonate pathway is dysregulated in numerous cancers; thus, they accumulate sufficient IPP amounts to potently activate Vδ2 cells [ 48 ]. Phosphoantigens are not recognised directly; rather, they merely cause conformational changes in butyrophilins 2A1 and 3A1 (BTN2A1 and BTN3A1), which can later be sensed by γδ T cells via TCR [ 36 , 37 , 55 , 56 ]. Additionally, Vδ2 and Vδ1 cells express CD16 (FcγRIII), and their cytotoxic response against certain cancers can be significantly enhanced by therapeutic monoclonal antibodies [ 57 , 58 , 59 ].…”

Regulation and Functions of Protumoral Unconventional T Cells in Solid Tumors

“…CD1d (Vδ1) CD1c viral glycoproteins [11] MR1 [12] CD1d [13] CD1d [9] TCR ligands Natural Unknown Cardiolipin Phycoerythrin [14] IPP, HMBPP (Vγ9Vδ2) Sulfatide and α-GalCer (Vδ1) EPCR (Vγ4Vδ5) [15] Microbial-derived vitamin B2 metabolites (5-OP-RU, 5-OE-RU) [16] α-GalCer Microbial α-derived glycolipids Ganglioside [17][18][19] Sulfatide, LPC, PG Hydrophobic peptides…”

“…Human Vγ9Vδ2 T cells respond to small phosphorylated metabolites (i.e., phosphoantigens (PAgs)) produced by both microbial and mammalian cells. PAg recognition by the γδTCR is dependent on butyrophilin (BTN) and butyrophilin-like (BTNL) molecules [ 11 ]. Foreign or self-derived PAgs interact with an intracellular domain of BTN3A1 to induce TCR binding [ 55 , 56 ].…”