{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:58:12Z","timestamp":1790647092201,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2007,12,1]],"date-time":"2007-12-01T00:00:00Z","timestamp":1196467200000},"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":[[2007,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The E3 ubiquitin ligase Cbl-b is a negative regulator of TCR signaling that: 1) sets the activation threshold for T cells; 2) is induced in anergic T cells; and 3) protects against autoimmunity. However, the role of Cbl-b in regulating CD8 T cell activation and functions during physiological T cell responses has not been systematically examined. Using the lymphocytic choriomeningitis virus infection model, we show that Cbl-b deficiency did not significantly affect the clonal expansion of virus-specific CD8 T cells. However, Cbl-b deficiency not only increased the steady-state cell surface expression levels of TCR and CD8 but also reduced Ag-induced down-modulation of cell surface TCR expression by effector CD8 T cells. Diminished Ag-stimulated TCR down-modulation and sustained Ag receptor signaling induced by Cbl-b deficiency markedly augmented IFN-\u03b3 production, which is known to require substantial TCR occupancy. By contrast, Cbl-b deficiency minimally affected cell-mediated cytotoxicity, which requires limited engagement of TCRs. Surprisingly, despite elevated expression of CD8 and reduced Ag-induced TCR down-modulation, the functional avidity of Cbl-b-deficient effector CD8 T cells was comparable to that of wild-type effectors. Collectively, these data not only show that Cbl-b-imposed constraint on TCR signaling has differential effects on various facets of CD8 T cell response but also suggest that Cbl-b might mitigate tissue injury induced by the overproduction of IFN-\u03b3 by CD8 T cells. These findings have implications in the development of therapies to bolster CD8 T cell function during viral infections or suppress T cell-mediated immunopathology.<\/jats:p>","DOI":"10.4049\/jimmunol.179.11.7233","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:01:40Z","timestamp":1397847700000},"page":"7233-7243","source":"Crossref","is-referenced-by-count":44,"title":["Cbl-b Regulates Antigen-Induced TCR Down-Regulation and IFN-\u03b3 Production by Effector CD8 T Cells without Affecting Functional Avidity"],"prefix":"10.1093","volume":"179","author":[{"given":"Mohammed","family":"Shamim","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Som G","family":"Nanjappa","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin Hemmila","family":"Plisch","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E","family":"LeBlanc","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Walent","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Svaren","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Seroogy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin , Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,12,1]]},"reference":[{"key":"2026012809355180200_R1","first-page":"1218","volume-title":"Science","year":"2003"},{"key":"2026012809355180200_R2","first-page":"907","volume-title":"Nat. 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