{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:19:01Z","timestamp":1788985141932,"version":"build-2803163510"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"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":[[2012,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8\u03b1+ dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression did not impair uptake of dying cells by CD8\u03b1+ dendritic cells or cross-presentation of cell-associated Ag to CD8+ T cells, suggesting overlapping function between Treml4 and other receptors in vivo. To further investigate Treml4 function, we took advantage of a newly generated mAb against Treml4 and engineered its H chain to express three different Ags (i.e., OVA, HIV GAGp24, and the extracellular domain of the breast cancer protein HER2). OVA directed to Treml4 was efficiently presented to CD8+ and CD4+ T cells in vivo. Anti\u2013Treml4-GAGp24 mAbs, given along with a maturation stimulus, induced Th1 Ag-specific responses that were not observed in Treml4 knockout mice. Also, HER2 targeting using anti-Treml4 mAbs elicited combined CD4+ and CD8+ T cell immunity, and both T cells participated in resistance to a transplantable tumor. Therefore, Treml4 participates in Ag presentation in vivo, and targeting Ags with anti-Treml4 Abs enhances immunization of otherwise naive mice.<\/jats:p>","DOI":"10.4049\/jimmunol.1102541","type":"journal-article","created":{"date-parts":[[2011,12,31]],"date-time":"2011-12-31T01:39:30Z","timestamp":1325295570000},"page":"1147-1155","source":"Crossref","is-referenced-by-count":34,"title":["Treml4, an Ig Superfamily Member, Mediates Presentation of Several Antigens to T Cells In Vivo, Including Protective Immunity to HER2 Protein"],"prefix":"10.1093","volume":"188","author":[{"given":"Hiroaki","family":"Hemmi","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"},{"name":"Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Laboratory for Host Defense, The Institute of Physical and Chemical Research Center for Allergy and Immunology , Tsurumi-ku, Yokohama, Kanagawa 230-0045 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeha","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Matos","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Fiorese","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashira","family":"Lubkin","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Zbytnuik","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Suda","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"},{"name":"Frontier Research Laboratories, Daiichi Sankyo Co., Ltd. , Edogawa-ku, Tokyo 134-8630 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Noda","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University , Tokyo 113-8510 ,","place":["Japan"]},{"name":"Global Center of Excellence Program for the International Research Center for Molecular Science in Tooth and Diseases, Tokyo Medical and Dental University , Tokyo 113-8510 ,","place":["Japan"]},{"name":"Hard Tissue Genome Research Center, Tokyo Medical and Dental University , Tokyo 113-8510 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneyasu","family":"Kaisho","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University , Suita, Osaka 565-0871 ,","place":["Japan"]},{"name":"Laboratory for Host Defense, The Institute of Physical and Chemical Research Center for Allergy and Immunology , Tsurumi-ku, Yokohama, Kanagawa 230-0045 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph M","family":"Steinman","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Idoyaga","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Physiology and Immunology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,2,1]]},"reference":[{"key":"2025032409484467600_r1","doi-asserted-by":"crossref","first-page":"R375","DOI":"10.1016\/j.cub.2009.03.032","article-title":"Necrosis: C-type lectins sense cell death","volume":"19","author":"Cambi","year":"2009","journal-title":"Curr. 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