2026-06-27T23:49:22Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/433442023-08-26T03:58:11Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Gil Calle, Juana Nelly author Busto, Elena M author Garcillán Goyoaga, Beatriz de author Chean, Carmen author García Rodríguez, María Cruz author Díaz Alderete, Andrea author Navarro, Joaquín author Reiné Gutiérrez, Jesús author Mencía, Ángeles author Gurbindo, Dolores author Beléndez, Cristina author Gordillo, Isabel author Duchniewicz, Marlena author Höhne, Kerstin author García Sánchez, Félix author Fernández Cruz, Eduardo author López Granados, Eduardo author Schamel, Wolfgang W.A. author Moreno Pelayo, Miguel A author Recio Hoyas, María José author Regueiro González-Barros, José Ramón 2023-06-20T01:08:49Z 2023-06-20T01:08:49Z 2011-10 0021-9738; 1558-8238 10.1172/JCI44254 https://hdl.handle.net/20.500.14352/43344 https://doi.org/10.1172/JCI44254 T cells recognize antigens via their cell surface TCR and are classified as either αβ or γδ depending on the variable chains in their TCR, α and β or γ and δ, respectively. Both αβ and γδ TCRs also contain several invariant chains, including CD3δ, which support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect a single T cell lineage, while mutations in the invariant chains would affect all T cells. Consistent with this, all CD3δ-deficient patients described to date showed a complete block in T cell development. However, CD3δ-KO mice have an αβ T cell–specific defect. Here, we report 2 unrelated cases of SCID with a selective block in αβ but not in γδ T cell development, associated with a new splicing mutation in the CD3D gene. The patients’ T cells showed reduced CD3D transcripts, CD3δ proteins, surface TCR, and early TCR signaling. Their lymph nodes showed severe T cell depletion, recent thymus emigrants in peripheral blood were strongly decreased, and the scant αβ T cells were oligoclonal. T cell–dependent B cell functions were also impaired, despite the presence of normal B cell numbers. Strikingly, despite the specific loss of αβ T cells, surface TCR expression was more reduced in γδ than in αβ T cells. Analysis of individuals with this CD3D mutation thus demonstrates the contrasting CD3δ requirements for αβ versus γδ T cell development and TCR expression in humans and highlights the diagnostic and clinical relevance of studying both TCR isotypes when a T cell defect is suspected. eng A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ−Tγδ+B+NK+ human SCID journal article URL https://docta.ucm.es/bitstreams/38c0d118-7649-4aeb-ae0a-fb54b4567491/download File MD5 592e1a008963ab9d771db46c68f30558 1702962 application/pdf j-clin-invest-2011.pdf URL https://docta.ucm.es/bitstreams/fe1b6cba-4d5a-43f5-90e1-1c6ccd5fc9f6/download File MD5 6d87bf69a7340cc8eb7fcc5cc8227772 59377 text/plain j-clin-invest-2011.pdf.txt