{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:03:57Z","timestamp":1791443037302,"version":"4.3.3"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"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":[[2000,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>X-linked lymphoproliferative syndrome (XLP) is an immunodeficiency characterized by life-threatening infectious mononucleosis and EBV-induced B cell lymphoma. The gene mutated in XLP encodes SLAM (signaling lymphocytic activation molecule-associated protein)-associated protein (SAP), a small SH2 domain-containing protein. SAP associates with 2B4 and SLAM, activating receptors expressed by NK and T cells, and prevents recruitment of SH2 domain-containing protein tyrosine phosphatase-2 SHP-2) to the cytoplasmic domains of these receptors. The phenotype of XLP may therefore result from perturbed signaling through SAP-associating receptors. We have addressed the functional consequence of SAP deficiency on 2B4-mediated NK cell activation. Ligating 2B4 on normal human NK cells with anti-2B4 mAb or interaction with transfectants bearing the 2B4 ligand CD48 induced NK cell cytotoxicity. In contrast, ligation of 2B4 on NK cells from a SAP-deficient XLP patient failed to initiate cytotoxicity. Despite this, CD2 or CD16-induced cytotoxicity of SAP-deficient NK cells was similar to that of normal NK cells. Thus, selective impairment of 2B4-mediated NK cell activation may contribute to the immunopathology of XLP.<\/jats:p>","DOI":"10.4049\/jimmunol.165.6.2932","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:30:49Z","timestamp":1398029449000},"page":"2932-2936","source":"Crossref","is-referenced-by-count":202,"title":["Cutting Edge: Functional Requirement for SAP in 2B4-Mediated Activation of Human Natural Killer Cells as Revealed by the X-Linked Lymphoproliferative Syndrome"],"prefix":"10.1093","volume":"165","author":[{"given":"Stuart G","family":"Tangye","sequence":"first","affiliation":[{"name":"Centenary Institute for Cancer Medicine and Cell Biology, and University of Sydney , New South Wales ,","place":["Australia"]},{"name":"Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology , Palo Alto, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph H","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology , Palo Alto, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis L","family":"Lanier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and the Cancer Research Institute, University of California , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim E","family":"Nichols","sequence":"additional","affiliation":[{"name":"Pediatric Oncology, Children\u2019s Hospital of Philadelpiha , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,9,15]]},"reference":[{"key":"2026020213124019600_R1","first-page":"875","volume-title":"Annu. 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