{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:48:16Z","timestamp":1793040496408,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>V\u03b39V\u03b42 effector T cells lyse cells in response to phosphorus-containing small molecules, providing primates a unique route to remove infected or malignant cells. Yet, the triggering mechanisms remain ill defined. We examined lysis mediated by human V\u03b39V\u03b42 effector T cells in response to the naturally occurring (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) or a synthetic cell-permeable prodrug, bis (pivaloyloxymethyl) (E)-4-hydroxy-3-methyl-but-2-enyl phosphonate. CD27+\/CD45RA\u2212 Th1-like effector cells killed K562 target cells through a mechanism that could be enhanced by either compound or TCR Ab and blocked by Src inhibition or butyrophilin 3 isoform A1 (BTN3A1) disruption. Pretreatment at 4\u00b0C decreased HMBPP-induced lysis but did not reduce lysis induced by bis (pivaloyloxymethyl) (E)-4-hydroxy-3-methyl-but-2-enyl phosphonate. Together, our results show that internalization of HMBPP into target cells is required for BTN3A1-dependent lysis by V\u03b39V\u03b42 effector T cells. The enhanced activity of the prodrug analog is due to its ability to bypass the pathways required for entry of HMBPP. These findings support an inside-out model of T cell triggering driven by small-molecule induction of BTN3A1.<\/jats:p>","DOI":"10.4049\/jimmunol.1501833","type":"journal-article","created":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T23:23:46Z","timestamp":1465255426000},"page":"419-428","source":"Crossref","is-referenced-by-count":43,"title":["HMBPP Analog Prodrugs Bypass Energy-Dependent Uptake To Promote Efficient BTN3A1-Mediated Malignant Cell Lysis by V\u03b39V\u03b42 T Lymphocyte Effectors"],"prefix":"10.1093","volume":"197","author":[{"given":"Ashley M","family":"Kilcollins","sequence":"first","affiliation":[{"name":"Department of Physiology and Neurobiology, University of Connecticut , Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Connecticut , Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hung Christine","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Connecticut , Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J","family":"Wiemer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Connecticut , Storrs, CT 06269"},{"name":"Institute for Systems Genomics, University of Connecticut , Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,7,15]]},"reference":[{"key":"2025030617463711900_r1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1365-3083.2007.01963.x","article-title":"Lysis of a broad range of epithelial tumour cells by human gamma delta T cells: involvement of NKG2D ligands and T-cell receptor- versus NKG2D-dependent recognition","volume":"66","author":"Wrobel","year":"2007","journal-title":"Scand. 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