Formato Vancouver:
Muñoz-Ruiz M, Pérez-Flores V, Garcillán B, Guardo AC, Mazariegos MS, Takada H et al. Human CD3γ, but not CD3δ,
haploinsufficiency differentially impairs γδ versus αβ surface TCR expression. BMC Immunol. 2013 Jan 21;14:3.

PMID: 23336327

Contiene 19 referencias

The T cell antigen receptors (TCR) of a beta and gamma delta T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, alpha beta or gamma delta TCR chains incorporate a CD3 delta epsilon dimer, then a CD3 delta epsilon dimer and finally a zeta zeta homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3 gamma and CD3 delta 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 alpha beta and gamma delta T cells from healthy donors carrying a single null or leaky mutation in CD3G (gamma(+/-)) or CD3D (delta(+/-), delta(+/leaky)) with that of normal controls. Results: Although the partial reduction in the intracellular availability of CD3 gamma or CD3 delta proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3 epsilon antibodies was significantly more decreased in gamma delta than in alpha beta T lymphocytes in CD3 gamma(+/-) individuals, whereas CD3 delta(+/-) and CD3 delta(+/leaky) donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface gamma delta TCR expression was more dependent on available CD3 gamma than surface alpha beta TCR expression. Conclusions: The results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3 gamma epsilon and CD3 delta epsilon dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3 gamma, but not of the homologous CD3 delta chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.