{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:23:27Z","timestamp":1772137407203,"version":"3.50.1"},"reference-count":32,"publisher":"Proceedings of the National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,10,23]]},"abstract":"<jats:p>\n                    Upon productive interaction of CD4 T cells with antigen-presenting cells (APCs), receptors and intracellular proteins translocate and form spatially segregated supramolecular activation clusters (SMACs). It is not known whether SMACs are required for CD8 T cell activation. CD8 T cells, unlike CD4 T cells, can be activated by a single peptide-MHC molecule, or by purified monovalent recombinant peptide-MHC molecules. We studied, by three-dimensional digital microscopy, cell conjugates of fresh\n                    <jats:italic>ex vivo<\/jats:italic>\n                    CD8 T cells (obtained from OT-1 mice, which are transgenic for T cell antigen receptor reactive with the complex of H-2K\n                    <jats:sup>b<\/jats:sup>\n                    and the ovalbumin octapeptide SIINFEKL) and peptide-pulsed APCs. Remarkably, even in T cell:APC conjugates that were formed in the presence of the lowest concentration of peptide that was sufficient to elicit T cell proliferation and IFN-\u03b3 production; the \u03b8 isoform of protein kinase C was clustered in a central SMAC, and lymphocyte function-associated antigen 1 and talin were clustered in the peripheral SMAC. Conjugation of T cells to APCs that were pulsed with concentrations of peptide smaller than that required to activate T cells was greatly reduced, and SMACs were not formed at all. APCs expressing mutant H-2K\n                    <jats:sup>b<\/jats:sup>\n                    (Lys\n                    <jats:sup>227<\/jats:sup>\n                    ) molecules that do not bind CD8 were unable to form stable conjugates with these T cells, even at high peptide concentrations. Thus, although CD8 and CD4 T cells may display different sensitivity to the concentration and oligomerization of surface receptors, SMACs are formed and seem to be required functionally in both cell types. However, unlike CD4 T cells, which can form SMACs without CD4, CD8 T cells from OT-1 transgenic mice depend on their coreceptor, CD8, for the proper formation of SMACs .\n                  <\/jats:p>","DOI":"10.1073\/pnas.221458898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"12624-12629","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":104,"title":["Formation of supramolecular activation clusters on fresh\n                    <i>ex vivo<\/i>\n                    CD8\n                    <sup>+<\/sup>\n                    T cells after engagement of the T cell antigen receptor and CD8 by antigen-presenting cells"],"prefix":"10.1073","volume":"98","author":[{"given":"Terry A.","family":"Potter","sequence":"first","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristie","family":"Grebe","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Freiberg","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Kupfer","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[2001,10,16]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/25764"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5483.1349"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80279-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/385083a0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.221"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5397.2266"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.10.040192.003241"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/356796a0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/337073a0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/384577a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80572-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/42523"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80635-4"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2118680"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/346574a0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(94)90079-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.4049\/jimmunol.154.2.567","volume":"154","author":"Kageyama 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