A leaky mutation in CD3D differentially affects ?? and ?? T cells and leads to a T??-T??+B+NK+ human SCID.
19.09.2011
Gil J, Busto EM, Garcillán B, Chean C, García-Rodríguez MC, Díaz-Alderete A, Navarro J, Reiné J, Mencía A, Gurbindo D, Beléndez C, Gordillo I, Duchniewicz M, Höhne K, García-Sánchez F, Fernández-Cruz E, López-Granados E, Schamel WW, Moreno-Pelayo MA, Recio MJ, Regueiro JR.
J Clin Invest. 2011 Oct 3;121(10):3872-6.
T cell receptor (TCR) of the immune system comprises the TCR?? CD3???? or the TCR?? CD3???? subunits, depending on the TCR isotype (?? TCR or ?? TCR, respectively). The CD3 subunits support expression of the complete TCR on the T cell surface. In this BIOSS publication we used the Drosophila S2 reconstitution system to test the requirements for the surface expression of the ?? TCR with mutant CD3? sequences that were derived from CD3? mutant patients. This was done in collaboration with the group of Jose Ramon Regueiro in Spain. Mutations in the CD3 chains are expected affect all T cells, since all CD3 chains are part of the ?? TCR and the ?? TCR (see above). In this publication, we describe two human cases of severe combined immunodeficiencies with a selective block in ?? but not in ?? T cell development, associated with a splicing mutation in the gene for CD3?. The patients’ T cells showed reduced early TCR signaling and their lymph nodes showed severe T
cell depletion. T cell–dependent B cell functions were impaired, although we found normal B cell numbers. Despite the specific reduction in ?? T cell numbers, surface TCR expression was more reduced in ?? T cells compared to ?? T cells. In conclusion, our analysis of patients with this CD3? mutation demonstrated the contrasting CD3? requirements for ?? versus ?? T cell development and TCR
expression. This highlights the diagnostic and clinical relevance of studying both TCR isotypes when a T cell defect is suspected.
