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

Gabrielle M. Siegers, Mahima Swamy, Edgar Fernández-Malavé, Susana Minguet, Sylvia Rathmann, Alberto C. Guardo, Verónica Pérez-Flores, Jose R. Regueiro, Balbino Alarcón, Paul Fisch, Wolfgang W.A. Schamel (Lead / Corresponding author)

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37 Citations (Scopus)

Abstract

The γδ T cell receptor for antigen (TCR) comprises the clonotypic TCRγδ, the CD3 (CD3γε and/or CD3δε), and the ζζ dimers. γδ T cells do not develop in CD3γ-deficient mice, whereas human patients lacking CD3γ have abundant peripheral blood γδ T cells expressing high γδ TCR levels. In an attempt to identify the molecular basis for these discordant phenotypes, we determined the stoichiometries of mouse and human γδ TCRs using blue native polyacrylamide gel electrophoresis and anti-TCR-specific antibodies. The γδ TCR isolated in digitonin from primary and cultured human γδ T cells includes CD3δ, with a TCRγδCD3ε2δγζ2 stoichiometry. In CD3γ-deficient patients, this may allow substitution of CD3γ by the CD3δ chain and thereby support γδ T cell development. In contrast, the mouse γδ TCR does not incorporate CD3δ and has a TCRγδCD3ε2γ 2ζ2 stoichiometry. CD3γ-deficient mice exhibit a block in γδ T cell development. A human, but not a mouse, CD3δ transgene rescues γδ T cell development in mice lacking both mouse CD3δ and CD3γ chains. This suggests important structural and/or functional differences between human and mouse CD3δ chains during γδ T cell development. Collectively, our results indicate that the different γδ T cell phenotypes between CD3γ-deficient humans and mice can be explained by differences in their γδ TCR composition. JEM

Original languageEnglish
Pages (from-to)2537-2544
Number of pages8
JournalJournal of Experimental Medicine
Volume204
Issue number11
DOIs
Publication statusPublished - 8 Oct 2007

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    • 37 Citations
    • 1 Comment/debate

    Erratum: Different composition of the human and the mouse γδ T cell receptor explains different phenotypes of CD3γ and CD3δ immunodeficiencies (Journal of Experimental Medicine (2007) 204, 11, (2537-2544))

    Siegers, G. M., Swamy, M., Fernández-Malavé, E., Minguet, S., Rathmann, S., Guardo, A. C., Pérez-Flores, V., Regueiro, J. R., Alarcón, B., Fisch, P. & Schamel, W. W. A., 26 Nov 2007, In : Journal of Experimental Medicine. 204, 12, 1 p., 3049.

    Research output: Contribution to journalComment/debate

    1 Citation (Scopus)

    Cite this

    Siegers, G. M., Swamy, M., Fernández-Malavé, E., Minguet, S., Rathmann, S., Guardo, A. C., Pérez-Flores, V., Regueiro, J. R., Alarcón, B., Fisch, P., & Schamel, W. W. A. (2007). Different composition of the human and the mouse γδ T cell receptor explains different phenotypes of CD3γ and CD3δ immunodeficiencies. Journal of Experimental Medicine, 204(11), 2537-2544. https://doi.org/10.1084/jem.20070782