Human CD3[gamma], but not CD3[delta], haploinsufficiency differentially impairs gamma delta versus alpha beta surface TCR expression

• Published in: BMC immunology 2013-01, Vol.14 (1), p.3-3
• Main Authors: Munoz-Ruiz, Miguel, Perez-Flores, Veronica, Garcillan, Beatriz, Guardo, Alberto C, Mazariegos, Marina S, Takada, Hidetoshi, Allende, Luis M, Kilic, Sara S, Sanal, Ozden, Roifman, Chaim M, Lopez-Granados, Eduardo, Recio, Maria J, Martinez-Naves, Eduardo, Fernandez-Malave, Edgar, Regueiro, Jose R
• Format: Article
• Language: English
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/1471-2172-14-3

Background: The T cell antigen receptors (TCR) of alpha 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 member of dimer, then a CD3 gamma member of 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] super(+/-)) or CD3D ([delta] super(+/-), [delta] super(+/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] super(+/-) individuals, whereas CD3[delta] super(+/-) and CD3[delta] super(+/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 member of and CD3 delta member of 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.