{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:27:38Z","timestamp":1790976458350,"version":"4.1.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"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":[[2011,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Resting human NK cells require a two-stage activation process that we have previously described as \u201cpriming\u201d and \u201ctriggering.\u201d NK-sensitive tumor cells provide both priming and triggering signals. NK-resistant tumors evade lysis, mostly by failure to prime; however, we recently reported a tumor cell line (CTV-1) that primes resting NK cells but fails to trigger lysis. In this article, we report two additional leukemia cell lines that prime NK cells but are resistant to lysis. Tumor-mediated NK priming is via CD2 binding to a ligand within CD15 on the tumor cell. NK-resistant RAJI cells became susceptible to NK lysis following transfection and expression of CD15. Blockade of CD15 on K562 cells or on CD15+ RAJI cells significantly inhibited lysis, as did blockade of CD2 on resting NK cells. NK priming via CD2 induced CD16 shedding, releasing CD3\u03b6 to the CD2, leading to its phosphorylation and the subsequent phosphorylation of linker for activation of T cells and STAT-5 and synthesis of IFN-\u03b3. Blockade of C-type lectin receptors significantly suppressed the tumor-mediated priming of NK cells, whereas blockade of Ig-superfamily\u2013like receptors had no effect at the NK-priming stage. Tumor priming of resting NK cells was irrespective of HLA expression, and blockade of HLA\u2013killer Ig-like receptor interactions did not influence the incidence or degree of priming. However, CD15\u2013CD2 interactions were critical for NK priming and were required, even in the absence of HLA-mediated NK inhibition. Tumor-mediated priming led to a sustained primed state, and the activated NK cells retained the ability to lyse NK-resistant tumors, even after cryopreservation.<\/jats:p>","DOI":"10.4049\/jimmunol.1101640","type":"journal-article","created":{"date-parts":[[2011,11,15]],"date-time":"2011-11-15T20:02:15Z","timestamp":1321387335000},"page":"6227-6234","source":"Crossref","is-referenced-by-count":38,"title":["Leukemic Priming of Resting NK Cells Is Killer Ig-like Receptor Independent but Requires CD15-Mediated CD2 Ligation and Natural Cytotoxicity Receptors"],"prefix":"10.1093","volume":"187","author":[{"given":"May","family":"Sabry","sequence":"first","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tsirogianni","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail A","family":"Bakhsh","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"North","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janani","family":"Sivakumaran","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Giannopoulos","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Mackinnon","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W","family":"Lowdell","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Free Hospital Campus, University College London Medical School , London NW3 2PF ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,12,15]]},"reference":[{"key":"2025032410521304100_r1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1182\/blood-2005-04-1351","article-title":"Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion","volume":"107","author":"Bryceson","year":"2006","journal-title":"Blood"},{"key":"2025032410521304100_r2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.4049\/jimmunol.178.1.85","article-title":"Tumor-primed human natural killer cells lyse NK-resistant tumor targets: evidence of a two-stage process in resting NK cell activation","volume":"178","author":"North","year":"2007","journal-title":"J. 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