An Update on the Molecular Basis of Phosphoantigen Recognition by V?9V?2 T Cells.

ABSTRACT: About 1-5% of human blood T cells are V?9V?2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose ?-chains contain a rearrangement of V?9 with JP (TRGV9JP or V?2J?1.2) and are paired with V?2 (TRDV2)-containing ?-chains. These TCRs respond to phosphoantigens (PAg) such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is found in many pathogens, and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. Until recently, these cells were believed to be restricted to primates, while no such cells are found in rodents. The identification of three genes pivotal for PAg recognition encoding for V?9, V?2, and butyrophilin (BTN) 3 in various non-primate species identified candidate species possessing PAg-reactive V?9V?2 T cells. Here, we review the current knowledge of the molecular basis of PAg recognition. This not only includes human V?9V?2 T cells and the recent discovery of BTN2A1 as V?9-binding protein mandatory for the PAg response but also insights gained from the identification of functional PAg-reactive V?9V?2 T cells and BTN3 in the alpaca and phylogenetic comparisons. Finally, we discuss models of the molecular basis of PAg recognition and implications for the development of transgenic mouse models for PAg-reactive V?9V?2 T cells.

SUBMITTER: Herrmann T 

PROVIDER: S-EPMC7348870 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature