{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:35:09Z","timestamp":1777451709932,"version":"3.51.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"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":[[2010,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>CD8+ CTLs are essential for effective immune defense against intracellular microbes and neoplasia. CTLs recognize short peptide fragments presented in association with MHC class I (MHCI) molecules on the surface of infected or dysregulated cells. Ag recognition involves the binding of both TCR and CD8 coreceptor to a single ligand (peptide MHCI [pMHCI]). The TCR\/pMHCI interaction confers Ag specificity, whereas the pMHCI\/CD8 interaction mediates enhanced sensitivity to Ag. Striking biophysical differences exist between the TCR\/pMHCI and pMHCI\/CD8 interactions; indeed, the pMHCI\/CD8 interaction can be &amp;gt;100-fold weaker than the cognate TCR\/pMHCI interaction. In this study, we show that increasing the strength of the pMHCI\/CD8 interaction by \u223c15-fold results in nonspecific, cognate Ag-independent pMHCI tetramer binding at the cell surface. Furthermore, pMHCI molecules with superenhanced affinity for CD8 activate CTLs in the absence of a specific TCR\/pMHCI interaction to elicit a full range of effector functions, including cytokine\/chemokine release, degranulation and proliferation. Thus, the low solution binding affinity of the pMHCI\/CD8 interaction is essential for the maintenance of CTL Ag specificity.<\/jats:p>","DOI":"10.4049\/jimmunol.0902398","type":"journal-article","created":{"date-parts":[[2010,2,26]],"date-time":"2010-02-26T21:31:19Z","timestamp":1267219879000},"page":"3357-3366","source":"Crossref","is-referenced-by-count":26,"title":["MHC Class I Molecules with Superenhanced CD8 Binding Properties Bypass the Requirement for Cognate TCR Recognition and Nonspecifically Activate CTLs"],"prefix":"10.1093","volume":"184","author":[{"given":"Linda","family":"Wooldridge","sequence":"first","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathew","family":"Clement","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Lissina","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily S J","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Ladell","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Ekeruche","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel E","family":"Hewitt","sequence":"additional","affiliation":[{"name":"Micronutrient Status Research Section, Medical Research Council Human Nutrition Research , Cambridge,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Laugel","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Gostick","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David K","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reno","family":"Debets","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center , Rotterdam,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cor","family":"Berrevoets","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Tumor Immunology, Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center , Rotterdam,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"},{"name":"Division of Immunology, Queensland Institute of Medical Research , Brisbane,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott R","family":"Burrows","sequence":"additional","affiliation":[{"name":"Division of Immunology, Queensland Institute of Medical Research , Brisbane,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew K","family":"Sewell","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity, and Biochemisty, Cardiff University , Cardiff"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,4,1]]},"reference":[{"key":"2026012806350115400_r1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev.immunol.16.1.523","article-title":"Ligand recognition by alpha beta T cell receptors.","volume":"16","author":"Davis","year":"1998","journal-title":"Annu. 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