{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T10:30:33Z","timestamp":1770892233284,"version":"3.50.1"},"reference-count":53,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,1,17]]},"abstract":"<jats:p>Recent data using MHC\/peptide tetramers and dimers suggests that the T cell coreceptors, CD4 and CD8, although important for T cell activation, do not play a direct role in facilitating T cell receptor (TCR) binding to multivalent MHC\/peptide ligands. Instead, a current model proposes that coreceptors are recruited only after a stable TCR\u2013MHC\/peptide complex has already formed and signaled. In contrast, we show using multimeric class I MHC\/peptide ligands that CD8 plays a critical (in some cases obligatory) role in antigen-specific TCR binding. T cell activation, measured by calcium mobilization, was induced by multimeric but not monomeric ligands and also showed CD8 dependency. Our analysis using anti-CD8 antibodies revealed that binding to different epitopes of CD8 can either block or augment TCR\u2013MHC\/peptide interaction. These effects on TCR binding to high-affinity agonist ligands were even more pronounced when binding to multimeric low-affinity ligands, including TCR antagonists, was studied. Our data have important implications for the role of CD8 in TCR binding to MHC\/peptide ligands and in T cell activation. In addition, our results argue against the view that multimeric MHC\/peptide ligands bind directly and solely to the TCR; rather, our data highlight a pivotal contribution of CD8 for this association.<\/jats:p>","DOI":"10.1084\/jem.191.2.335","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"335-346","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":192,"title":["Critical Role for Cd8 in T Cell Receptor Binding and Activation by Peptide\/Major Histocompatibility Complex Multimers"],"prefix":"10.1084","volume":"191","author":[{"given":"Mark A.","family":"Daniels","sequence":"first","affiliation":[{"name":"aCenter for Immunology, Department of Lab Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455"}]},{"given":"Stephen C.","family":"Jameson","sequence":"additional","affiliation":[{"name":"aCenter for Immunology, Department of Lab Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455"}]}],"member":"291","reference":[{"key":"2023072509034910100_R1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1146\/annurev.iy.10.040192.003241","article-title":"The T cell receptor as a multicomponent signalling machineCD4\/CD8 coreceptors and CD45 in T cell activation","volume":"10","author":"Janeway","year":"1992","journal-title":"Annu. 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