Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression

BMC Immunology

José R Regueiro¹  Edgar Fernández-Malavé¹  Eduardo Martínez-Naves⁶  María J Recio¹  Eduardo López-Granados⁷  Chaim M Roifman³  Ozden Sanal⁴  Sara S Kilic⁵  Luis M Allende²  Hidetoshi Takada⁸  Marina S Mazariegos¹  Alberto C Guardo⁶  Beatriz Garcillán¹  Verónica Pérez-Flores⁶  Miguel Muñoz-Ruiz¹ 

[1] 12 de Octubre Institute of Health Research, Madrid, Spain;Inmunología, Hospital 12 de Octubre, Madrid, 28041, Spain;Immunology and Allergy, Hospital for Sick Children, University of Toronto, Toronto, Canada;Immunology Division, Hacettepe University, Children’s Hospital, Ankara, Turkey;Pediatric Immunology, Uludag University, Görükle-Bursa, Turkey;Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, 28040, Spain;La Paz University Hospital, Madrid, Spain;Departament of Pediatrics, Kyushu University, Higashi-ku, Fukuoka, Japan

关键词: Haploinsufficiency;    CD3;    T cells;   

Others  :  1077846
DOI  :  10.1186/1471-2172-14-3

 received in 2012-09-21, accepted in 2013-01-16,  发布年份 2013

【 摘 要 】

Background

The T cell antigen receptors (TCR) of αβ and γδ T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, αβ or γδ TCR chains incorporate a CD3δε dimer, then a CD3γε dimer and finally a ζζ homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3γ and CD3δ 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 αβ and γδ T cells from healthy donors carrying a single null or leaky mutation in CD3G (γ^+/−) or CD3D (δ^+/−, δ^+/leaky) with that of normal controls.

Results

Although the partial reduction in the intracellular availability of CD3γ or CD3δ proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3ε antibodies was significantly more decreased in γδ than in αβ T lymphocytes in CD3γ^+/− individuals, whereas CD3δ^+/− and CD3δ^+/leaky donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface γδ TCR expression was more dependent on available CD3γ than surface αβ TCR expression.

Conclusions

The results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3γε and CD3δε dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3γ, but not of the homologous CD3δ chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.

【 授权许可】

   
2013 Muñoz-Ruiz et al; licensee BioMed Central Ltd.

【 图 表 】

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