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RASGRP1 is a T\u2010lymphocyte\u2010specific nucleotide exchange factor known to activate the pathway of MAP kinases (MAPK). A deleterious homozygous mutation in\n                    <jats:italic>RASGRP1<\/jats:italic>\n                    leading to the loss RASGRP1 expression was identified in two siblings who both developed a persistent EBV infection leading to Hodgkin lymphoma. RASGRP1\u2010deficient T cells exhibited defective MAPK activation and impaired proliferation that was restored by expression of wild\u2010type RASGRP1. Similar defects were observed in T cells from healthy individuals when RASGRP1 was downregulated. RASGRP1\u2010deficient T cells also exhibited decreased CD27\u2010dependent proliferation toward CD70\u2010expressing EBV\u2010transformed B cells, a crucial pathway required for expansion of antigen\u2010specific T cells during anti\u2010EBV immunity. Furthermore, RASGRP1\u2010deficient T cells failed to upregulate CTPS1, an important enzyme involved in DNA synthesis. These results show that RASGRP1 deficiency leads to susceptibility to EBV infection and demonstrate the key role of RASGRP1 at the crossroad of pathways required for the expansion of activated T\u00a0lymphocytes.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201708292","type":"journal-article","created":{"date-parts":[[2017,12,27]],"date-time":"2017-12-27T20:10:45Z","timestamp":1514405445000},"page":"188-199","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Loss of RASGRP1 in humans impairs T\u2010cell expansion leading to Epstein\u2010Barr virus susceptibility"],"prefix":"10.1038","volume":"10","author":[{"given":"Sarah","family":"Winter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Boutboul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Lenoir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabah","family":"Boudjemaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Petit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Capucine","family":"Picard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Leverger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8238-4391","authenticated-orcid":false,"given":"Sylvain","family":"Latour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,8]]},"reference":[{"key":"BFEMMM201708292_CR1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1084\/jem.20160849","volume":"214","author":"H Abolhassani","year":"2017","unstructured":"Abolhassani H, Edwards ES, Ikinciogullari A, Jing H, Borte S, Buggert M, Du L, Matsuda\u2010Lennikov M, Romano R, Caridha R et\u00a0al (2017) Combined immunodeficiency and Epstein\u2010Barr virus\u2010induced B cell malignancy in humans with inherited CD70 deficiency. 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