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Here, we used pMHCI tet to enumerate CD8 T cells specific for the immunodominant gp33 epitope of lymphocytic choriomeningitis virus glycoprotein (GP) in mice transgenically engineered to express high levels of GP as a self\u2010antigen in the thymus. In GP\u2010transgenic mice (GP<jats:sup>+<\/jats:sup>), monoclonal P14 TCR<jats:sup>+<\/jats:sup> CD8 T cells that express a GP\u2010specific TCR could not be detected by gp33\/D<jats:sup>b<\/jats:sup>\u2010tet staining, indicative of their complete intrathymic deletion. By contrast, in the same GP<jats:sup>+<\/jats:sup> mice, substantial numbers of polyclonal CD8 T cells identifiable by gp33\/D<jats:sup>b<\/jats:sup>\u2010tet were present. The gp33\u2010tet staining profiles of polyclonal T cells from GP<jats:sup>+<\/jats:sup> and GP\u2010negative (GP<jats:sup>\u2212<\/jats:sup>) mice were overlapping, but mean fluorescence intensities were \u223c15% lower in cells from GP<jats:sup>+<\/jats:sup> mice. Remarkably, the gp33\u2010tet<jats:sup>+<\/jats:sup> T cells in GP<jats:sup>+<\/jats:sup> mice failed to clonally expand after lymphocytic choriomeningitis virus infection, whereas those of GP<jats:sup>\u2212<\/jats:sup> mice did so. In Nur77<jats:sup>GFP<\/jats:sup>\u2010reporter mice, dose\u2010dependent responses to gp33 peptide\u2010induced TCR stimulation revealed that gp33\u2010tet<jats:sup>+<\/jats:sup> T cells with high\u00a0ligand sensitivity are lacking in GP<jats:sup>+<\/jats:sup> mice. Hence, pMHCI tet staining identifies self\u2010specific CD8 T cells but tends to overestimate the number of truly self\u2010reactive cells.<\/jats:p>","DOI":"10.1002\/eji.202350402","type":"journal-article","created":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T09:50:12Z","timestamp":1684057812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["MHC I tetramer staining tends to overestimate the number of functionally relevant self\u2010reactive CD8 T cells in the preimmune repertoire"],"prefix":"10.1002","volume":"53","author":[{"given":"Hanspeter","family":"Pircher","sequence":"first","affiliation":[{"name":"Department of Developmental Immunology Max Planck Institute of Immunobiology and Epigenetics  Freiburg im Breisgau Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel D.","family":"Pinschewer","sequence":"additional","affiliation":[{"name":"Division of Experimental Virology Department of Biomedicine University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Boehm","sequence":"additional","affiliation":[{"name":"Department of Developmental Immunology Max Planck Institute of Immunobiology and Epigenetics  Freiburg im Breisgau Germany"},{"name":"Faculty of Medicine University of Freiburg  Freiburg im Breisgau Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5284.94"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"171311","DOI":"10.1002\/cpim.14","article-title":"MHC\u2010peptide tetramers to visualize antigen\u2010specific T cells","volume":"115","author":"Altman J. 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