%0 Journal Article
%T Human CD3¦Ã, but not CD3¦Ä, haploinsufficiency differentially impairs ¦Ã¦Ä versus ¦Á¦Â surface TCR expression
%A Mu£¿oz-Ruiz Miguel
%A P¨¦rez-Flores Ver¨®nica
%A Garcill¨¢n Beatriz
%A Guardo Alberto C
%J BMC Immunology
%D 2013
%I BioMed Central
%R 10.1186/1471-2172-14-3
%X Background The T cell antigen receptors (TCR) of ¦Á¦Â and ¦Ã¦Ä T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, ¦Á¦Â or ¦Ã¦Ä TCR chains incorporate a CD3¦Ä¦Å dimer, then a CD3¦Ã¦Å dimer and finally a ¦Æ¦Æ homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3¦Ã and CD3¦Ä proteins would thus be expected to have a similar impact in the assembly and surface expression of both TCR isotypes. To test this hypothesis, we compared the surface TCR expression of primary ¦Á¦Â and ¦Ã¦Ä T cells from healthy donors carrying a single null or leaky mutation in CD3G (¦Ã+/ ) or CD3D (¦Ä+/ , ¦Ä+/leaky) with that of normal controls. Results Although the partial reduction in the intracellular availability of CD3¦Ã or CD3¦Ä proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3¦Å antibodies was significantly more decreased in ¦Ã¦Ä than in ¦Á¦Â T lymphocytes in CD3¦Ã+/  individuals, whereas CD3¦Ä+/  and CD3¦Ä+/leaky donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface ¦Ã¦Ä TCR expression was more dependent on available CD3¦Ã than surface ¦Á¦Â TCR expression. Conclusions The results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3¦Ã¦Å and CD3¦Ä¦Å dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3¦Ã, but not of the homologous CD3¦Ä chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.
%K T cells
%K CD3
%K Haploinsufficiency
%U http://www.biomedcentral.com/1471-2172/14/3