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Cell Dev. Biol."],"abstract":"<jats:p>The human \u03b1\u03b2 T-cell receptor (TCR) is composed of a variable heterodimer (TCR\u03b1\u03b2) and three invariant dimers (CD3\u03b3\u03b5, CD3\u03b4\u03b5, and \u03b6\u03b6\/CD247<jats:sub>2<\/jats:sub>). The role of each invariant chain in the stepwise interactions among TCR chains along the assembly is still not fully understood. Despite the high sequence homology between CD3\u03b3 and CD3\u03b4, the clinical consequences of the corresponding immunodeficiencies (ID) in humans are very different (mild and severe, respectively), and mouse models do not recapitulate findings in human ID. To try to understand such disparities, we stably knocked down (KD)<jats:italic>CD3D<\/jats:italic>or<jats:italic>CD3G<\/jats:italic>expression in the human Jurkat T-cell line and analyzed comparatively their impact on TCR\u03b1\u03b2 assembly, transport, and surface expression. The results indicated that TCR ensembles were less stable and CD3\u03b5 levels were lower when CD3\u03b3, rather than CD3\u03b4, was scarce. However, both defective TCR ensembles were strongly retained in the ER, lacked \u03b6\u03b6\/CD247<jats:sub>2<\/jats:sub>, and barely reached the T-cell surface (&amp;lt;11% of normal controls) in any of the<jats:italic>CD3<\/jats:italic>KD cells. This is in sharp contrast to human CD3\u03b3 ID, whose mature T cells express higher levels of surface TCR (&amp;gt;30% vs. normal controls).<jats:italic>CD3<\/jats:italic>KD of human T-cell progenitors followed by mouse fetal thymus organ cultures showed high plasticity in emerging immature polyclonal T lymphocytes that allowed for the expression of significant TCR levels which may then signal for survival in CD3\u03b3, but not in CD3\u03b4 deficiency, and explain the immunological and clinical disparities of such ID cases.<\/jats:p>","DOI":"10.3389\/fcell.2021.608490","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T07:39:10Z","timestamp":1624606750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["CD3G or CD3D Knockdown in Mature, but Not Immature, T Lymphocytes Similarly Cripples the Human TCR\u03b1\u03b2 Complex"],"prefix":"10.3389","volume":"9","author":[{"given":"Beatriz","family":"Garcill\u00e1n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Fuentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana V.","family":"Marin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca F.","family":"Megino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Chacon-Arguedas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina S.","family":"Mazariegos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Jim\u00e9nez-Reinoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Mu\u00f1oz-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel G.","family":"Laborda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula P.","family":"C\u00e1rdenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Fern\u00e1ndez-Malav\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria L.","family":"Toribio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R.","family":"Regueiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/nri1330","article-title":"Jurkat T cells and development of the T-cell receptor signalling paradigm.","volume":"4","author":"Abraham","year":"2004","journal-title":"Nat. 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