{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T16:39:59Z","timestamp":1758818399903},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:00:00Z","timestamp":1497916800000},"content-version":"vor","delay-in-days":842,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["2R44CA162582-02"],"award-info":[{"award-number":["2R44CA162582-02"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The protein <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 protects cells from complement attack by regulating cleavage of C3b and C3d. <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 also regulates the adaptive immune response by controlling T\u2010cell activation and differentiation. Co\u2010engagement of the T\u2010cell receptor and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 notably drives T\u2010cell differentiation by switching production of interferon\u2010<jats:italic>\u03b3<\/jats:italic> to secretion of anti\u2010inflammatory interleukin\u201010. This regulatory pathway is altered in several chronic inflammatory diseases, highlighting its key role for immune homeostasis. The manipulation of the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 pathway may therefore provide a powerful means to regulate immune responses. Herein, we investigated the effect of recombinant proteins derived from the fibre knob of the adenovirus serotype 35 (Ad35) that uses <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 as its entry receptor, on human T\u2010cell activation. We compared the effects of Ad35K++, engineered to exhibit enhanced affinity to <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46, and of Ad35K\u2212, mutated in the binding site for <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46. Ad35K++ profoundly affects T\u2010cell activation by decreasing the levels of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>46 at the surface of primary T cells, and impairing T\u2010cell co\u2010activation, shown by decreased <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25 expression, reduced proliferation and lower secretion of interleukin\u201010 and interferon\u2010<jats:italic>\u03b3<\/jats:italic>. In contrast, Ad35K\u2212 acts a potent co\u2010activator of T cells, enhancing T\u2010cell proliferation and cytokine production. These data show that recombinant Ad35 proteins are potent modulators of human T\u2010cell activation, and support their further development as potential drugs targeting T\u2010cell responses.<\/jats:p>","DOI":"10.1111\/imm.12391","type":"journal-article","created":{"date-parts":[[2014,9,22]],"date-time":"2014-09-22T16:25:51Z","timestamp":1411403151000},"page":"453-460","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Recombinant Ad35 adenoviral proteins as potent modulators of human T\u2010cell activation"],"prefix":"10.1111","volume":"144","author":[{"given":"Joanne","family":"Hay","sequence":"first","affiliation":[{"name":"MRC Centre for Inflammation Research University of Edinburgh Queen's Medical Research Institute Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darrick","family":"Carter","sequence":"additional","affiliation":[{"name":"PAI Life Sciences Inc. Seattle WA USA"},{"name":"Compliment Corp. Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Lieber","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Washington Seattle WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne L.","family":"Astier","sequence":"additional","affiliation":[{"name":"MRC Centre for Inflammation Research University of Edinburgh Queen's Medical Research Institute Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.163.4.837"},{"key":"e_1_2_8_3_1","first-page":"685","article-title":"The molecular basis of CD46 polymorphic expression and demonstration of a protective role against lysis by xenosera","volume":"24","author":"Loveland B","year":"1992","journal-title":"Transplant 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