{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T14:54:33Z","timestamp":1773240873409,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":3273,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1996,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A considerable fraction of T cells express two distinct T cell receptors (TCR), mainly due to expression of two TCR \u03b1 chains. It has been suggested that such dual\u2010TCR cells could have a role in autoimmunity. However, as such cells express less of each TCR, they could be less sensitive to their physiological ligand, <jats:italic>i.e<\/jats:italic>. peptide plus major histocompatibility complex molecules (MHC). We tested this hypothesis in a transgenic TCR model in which most T cells express different amounts of the transgene\u2010encoded TCR, due to expression of endogenous TCR \u03b1 chains. Five Th1 clones derived from \u03bb2<jats:sup>315<\/jats:sup> immunoglobulin light chain\u2010specific TCR\u2010transgenic mice expressed different levels of the transgene\u2010encoded TCR, ranging from \u223c 10000 to \u223c 50000 TCR per cell. Cytosolic Ca<jats:sup>2+<\/jats:sup> mobilization in single T cells from these clones elicited by \u03bb2<jats:sup>315<\/jats:sup> peptide\u2010pulsed, I\u2010E<jats:sup>d<\/jats:sup>\u2010expressing antigen\u2010presenting cells, correlated linearly with the relative transgene\u2010encoded TCR expression. The peptide requirement for half\u2010maximal T cell proliferation showed a similar correlation, with low TCR levels requiring higher peptide concentration. Corroborative evidence was obtained by deployment of short\u2010term polyclonal CD4<jats:sup>+<\/jats:sup> lines from TCR\u2010transgenic mice. Such lines had reduced early (Ca<jats:sup>2+<\/jats:sup> mobilization) and late (lymphokine and proliferation) responses, compared with T cell lines from recombination\u2010deficient TCR\u2010transgenic severe combined immunodeficiency mice (which express only a single transgene\u2010encoded TCR). Taken together, the Ca<jats:sup>2+<\/jats:sup> responses increase gradually with increasing TCR expression per cell, similar to the previously described analog Ca<jats:sup>2+<\/jats:sup> signaling elicited by increasing amounts of peptide\/MHC [R\u00f8tnes et al., <jats:italic>Eur. J. Immunol<\/jats:italic>. 1994. <jats:italic>24<\/jats:italic>: 851]. Surprisingly small reductions in TCR expression per cell reduce T cell responsiveness. This suggests that dual\u2010TCR T cells are immunologically less effective than single\u2010TCR T cells.<\/jats:p>","DOI":"10.1002\/eji.1830261211","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T01:29:25Z","timestamp":1172798965000},"page":"2876-2884","source":"Crossref","is-referenced-by-count":31,"title":["Dual T cell receptor T cells have a decreased sensitivity to physiological ligands due to reduced density of each T cell receptor"],"prefix":"10.1002","volume":"26","author":[{"given":"Erik","family":"Blichfeldt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludvig Andr\u00e9","family":"Munthe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Sigurd","family":"R\u00f8tnes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjarne","family":"Bogen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/334395a0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90334-4"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb26659.x"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.161.3.446"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/361315a0"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90179-5"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/364809a0"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3120001"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2873"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2783497"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-7952(05)80011-4"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950170605"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240412"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.4049\/jimmunol.148.9.2643","volume":"148","author":"Donnadieu E.","year":"1992","journal-title":"J. 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