02588nas a2200181   4500000000100000008004100001100001600042700001900058700001400077700001400091700001500105245015800120856008000278300000800358490000600366520202000372022001402392       2018                            d1 aFichtner AS1 aKarunakaran MM1 aStarick L1 aTruman RW1 aHerrmann T00aThe armadillo (Dasypus novemcinctus): A witness but not a functional example for the emergence of the butyrophilin 3/Vγ9Vδ2 system in placental mammals  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829056/pdf/fimmu-09-00265.pdf  a2650 v93 a<p>1-5% of human blood T cells are Vγ9Vδ2 T cells whose T cell receptor (TCR) contain arearrangement and acomprising Vδ2-chain. They respond to phosphoantigens (PAgs) like isopentenyl pyrophosphate or (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP) in a butyrophilin 3 (BTN3)-dependent manner and may contribute to the control of mycobacterial infections. These cells were thought to be restricted to primates, but we demonstrated by analysis of genomic databases that, andgenes coevolved and emerged together with placental mammals. Furthermore, we identified alpaca () as species with typical Vγ9Vδ2 TCR rearrangements and currently aim to directly identify Vγ9Vδ2 T cells and BTN3. Other candidates to study this coevolution are the bottlenose dolphin () and the nine-banded armadillo () with genomic sequences encoding open reading frames for, and the extracellular part of. Dolphins have been shown to express Vγ9- and Vδ2-like TCR chains and possess a predicted-like gene homologous to human. The other candidate, the armadillo, is of medical interest since it serves as a natural reservoir for. In this study, we analyzed the armadillo genome and found evidence for multiple non-functionalgenes including genomic context which closely resembles the organization of the human, alpaca, and dolphinloci. However, notranscript could be detected in armadillo cDNA. Additionally, attempts to identify a functionalrearrangementPCR failed. In contrast, completegene segments preferentially rearranged with ahomolog were cloned and co-expressed with a human Vγ9-chain in murine hybridoma cells. These cells could be stimulated by immobilized anti-mouse CD3 antibody but not with human RAJI-RT1Bcells and HMBPP. So far, the lack of expression ofrearrangements andrenders the armadillo an unlikely candidate species for PAg-reactive Vγ9Vδ2 T cells. This is in line with the postulated coevolution of the three genes, where occurrence of Vγ9Vδ2 TCRs coincides with a functional BTN3 molecule.</p>
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