Different composition of the human and the mouse γδ T cell receptor explains different phenotypes of CD3γ and CD3δ immunodeficiencies

• DOI: 10.1084/jem.20070782
• Publication Date: 2007-10-09T00:33:32Z
• Authors: Gabrielle M. Siegers; Mahima Swamy; Edgar Fernández-...; Susana Minguet; Sylvia Rathmann; Alberto C. Guardo; Verónica Pérez-...; Jose R. Regueiro; Balbino Alarcón; Paul Fisch; Wolfgang W.A. Sch...
• Keywords: Adult; Mice, Knockout; 0301 basic medicine; 570; 0303 health sciences; CD3 Complex; T-Lymphocytes; 610; Mice, Transgenic; Receptors, Antigen, T-Cell, gamma-delta; Corrections; Clone Cells; name=Immunology and Allergy; Mice; 03 medical and health sciences; Reference Values; /dk/atira/pure/subjectarea/asjc/2700/2723; Brief Definitive Reports; Animals; Humans; name=Immunology; Lymphocyte Count; /dk/atira/pure/subjectarea/asjc/2400/2403

The γδ T cell receptor for antigen (TCR) comprises the clonotypic TCRγδ, CD3 (CD3γε and/or CD3δε), and ζζ dimers. cells do not develop in CD3γ-deficient mice, whereas human patients lacking CD3γ have abundant peripheral blood expressing high TCR levels. In an attempt to identify molecular basis these discordant phenotypes, we determined stoichiometries of mouse TCRs using blue native polyacrylamide gel electrophoresis anti-TCR–specific antibodies. isolated digitonin from primary cultured includes CD3δ, with a TCRγδCD3ε2δγζ2 stoichiometry. patients, this may allow substitution by CD3δ chain thereby support development. contrast, does incorporate has TCRγδCD3ε2γ2ζ2 mice exhibit block A human, but mouse, transgene rescues development both chains. This suggests important structural functional differences between chains during Collectively, our results indicate that different phenotypes humans can be explained their composition.