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- Title
Human CD3?, but not CD3d, haploinsufficiency differentially impairs ?d versus aß surface TCR expression.
- Authors
Muñoz-Ruiz, Miguel; Pérez-Flores, Verónica; Garcillán, Beatriz; Guardo, Alberto C.; Mazariegos, Marina S.; Takada, Hidetoshi; Allende, Luis M.; Kilic, Sara S.; Sanal, Ozden; Roifman, Chaim M.; López-Granados, Eduardo; Recio, María J.; Martínez-Naves, Eduardo; Fernández-Malavé, Edgar; Regueiro, José R.
- Abstract
Background: The T cell antigen receptors (TCR) of aß and ?d T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, aß or ?d TCR chains incorporate a CD3de dimer, then a CD3?e dimer and finally a ?? homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3? and CD3d 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 aß and ?d T cells from healthy donors carrying a single null or leaky mutation in CD3G (?+/-) or CD3D (d+/-, d+/leaky) with that of normal controls. Results: Although the partial reduction in the intracellular availability of CD3? or CD3d proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3e antibodies was significantly more decreased in ?d than in aß T lymphocytes in CD3?+/- individuals, whereas CD3d+/- and CD3d+/leaky donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface ?d TCR expression was more dependent on available CD3? than surface aß TCR expression. Conclusions: The results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3?e and CD3de dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3?, but not of the homologous CD3d chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.
- Subjects
CD3 antigen; T cell receptors; GENE expression; GENETIC mutation; LIVER diseases; STOICHIOMETRY; IMMUNOGLOBULINS; GENETICS
- Publication
BMC Immunology, 2013, Vol 14, Issue 1, p1
- ISSN
1471-2172
- Publication type
Article
- DOI
10.1186/1471-2172-14-3