Alpaca (Vicugna pacos), the first nonprimate species with a phosphoantigen-reactive Vγ9Vδ2 T cell subset.

Proceedings of the National Academy of Sciences of the United States of America
Alina Suzann FichtnerThomas Herrmann

Abstract

Vγ9Vδ2 T cells are a major γδ T cell population in the human blood expressing a characteristic Vγ9JP rearrangement paired with Vδ2. This cell subset is activated in a TCR-dependent and MHC-unrestricted fashion by so-called phosphoantigens (PAgs). PAgs can be microbial [(E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate, HMBPP] or endogenous (isopentenyl pyrophosphate, IPP) and PAg sensing depends on the expression of B7-like butyrophilin (BTN3A, CD277) molecules. IPP increases in some transformed or aminobisphosphonate-treated cells, rendering those cells a target for Vγ9Vδ2 T cells in immunotherapy. Yet, functional Vγ9Vδ2 T cells have only been described in humans and higher primates. Using a genome-based study, we showed in silico translatable genes encoding Vγ9, Vδ2, and BTN3 in a few nonprimate mammalian species. Here, with the help of new monoclonal antibodies, we directly identified a T cell population in the alpaca (Vicugna pacos), which responds to PAgs in a BTN3-dependent fashion and shows typical TRGV9- and TRDV2-like rearrangements. T cell receptor (TCR) transductants and BTN3-deficient human 293T cells reconstituted with alpaca or human BTN3 or alpaca/human BTN3 chimeras showed that alpaca Vγ9Vδ2 TCRs recognize PAg in ...Continue Reading

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Citations

Apr 25, 2020·Immunology and Cell Biology·Matthias Eberl
Jun 13, 2020·Cells·Thomas HerrmannMohindar Murugesh Karunakaran
Jun 9, 2020·Frontiers in Cellular and Infection Microbiology·Jennifer A Juno, Stephen J Kent
Jul 28, 2020·Cellular & Molecular Immunology·Malte Deseke, Immo Prinz
Oct 6, 2020·Immunological Reviews·Adam P UldrichDale I Godfrey
Nov 5, 2020·Immunological Reviews·Maria PapadopoulouDavid Vermijlen
Mar 23, 2021·Molecular Immunology·Swarali S Kulkarni, Darryl Falzarano
Jul 24, 2021·Scientific Reports·Bjoern PetersenGregor Meyers
Aug 28, 2021·Nature Reviews. Nephrology·Hannah KaminskiMatthias Eberl

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