T cell receptor-alpha beta lacking the beta-chain V domain can be expressed at the cell surface but prohibits T cell maturation.

Ossendorp, Ferry; Jacobs, Heinz; Horst, G.; Vries, Evert de; Berns, Anton; Borst, J.

doi:10.4049/jimmunol.148.12.3714

Cited by 26 publications

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CD3 components at the surface of pro‐T cells can mediate pre‐T cell development in vivo

et al. 1994

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Developmentally arrested pro-T cells (CD4-8-, IL-2R+, HSA++) of RAG-1-deficient mice appear to express low levels of CD3 molecules in the absence of T cell receptor (TcR) chains at their surface, while developmentally arrested pre-T cells of TcR alpha-deficient mice express low levels of a disulfide-linked TcR beta chain in association with CD3 molecules. Cross-linking of the CD3 modules on pro-T cells of RAG-1-/- mice in vivo, with either of two different CD3 epsilon-specific monoclonal antibodies, induces differentiation of these pro-T cells into pre-T cells (CD4+8+, IL-2R-, HSA+), concomitant with a rapid expansion of the thymic T cell compartment, up to 175-fold within 12 days. The same effects can be produced by introduction of a mutant TcR beta transgene lacking most of the variable domain (delta V-TcR beta) into the RAG-1-/- background. These experiments suggest that cross-linking of the CD3 modules on pro-T cells mimics the signaling function expected of the pre-TcR complex, which is found at the surface of pre-T cells prior to functional TcR alpha gene rearrangement. The variable domain of the TcR beta chain is apparently not essential for inducing these aspects of T cell development.

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CD3 components at the surface of pro‐T cells can mediate pre‐T cell development in vivo

et al. 1994

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αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain

et al. 1997

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Commitment of the alpha beta and gamma delta T cell lineages within the thymus has been studied in T cell receptor (TCR)-transgenic and TCR mutant murine strains. TCR gamma delta-transgenic or TCR beta knockout mice, both of which are unable to generate TCR alpha beta-positive T cells, develop phenotypically alpha beta-like thymocytes in significant proportions. We provide evidence that in the absence of functional TCR beta protein, the gamma delta TCR can promote the development of alpha beta-like thymocytes, which, however, do not expand significantly and do not mature into gamma delta T cells. These results show that commitment to the alpha beta lineage can be determined independently of the isotype of the TCR, and suggest that alpha beta versus gamma delta T cell lineage commitment is principally regulated by mechanisms distinct from TCR-mediated selection. To accommodate our data and those reported previously on the effect of TCR gamma and delta gene rearrangements on alpha beta T cell development, we propose a model in which lineage commitment occurs independently of TCR gene rearrangement.

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T cell development in mice lacking the CD3-zeta/eta gene.

et al. 1993

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The CD3‐zeta and CD3‐eta polypeptides are two of the components of the T cell antigen receptor (TCR) which contribute to its efficient cell surface expression and account for part of its transducing capability. CD3‐zeta and CD3‐eta result from the alternative splicing of a single gene designated CD3‐zeta/eta. To evaluate the role of these subunits during T cell development, we have produced mice with a disrupted CD3‐zeta/eta gene. The analysis of thymocyte populations from the CD3‐zeta/eta‐/− homozygous mutant mice revealed that they have a profound reduction in the surface levels of TCR complexes and that the products of the CD3‐zeta/eta gene appear to be needed for the efficient generation and/or survival of CD4+CD8+ thymocytes. Despite the almost total absence of mature single positive thymocytes, the lymph nodes from zeta/eta‐/− mice were found to contain unusual CD4+CD8‐ and CD4‐CD8+ single positive cells which were CD3‐. In contrast to the situation observed in the thymus, the thymus‐independent gut intraepithelial lymphocytes present in zeta/eta‐/− mice do express TCR complexes on their surface and these are associated with Fc epsilon RI gamma homodimers. These results establish an essential role for the CD3‐zeta/eta gene products during intrathymic T cell differentiation and further emphasize the difference between conventional T cells and thymus‐independent gut intraepithelial lymphocytes.

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T cell receptor-alpha beta lacking the beta-chain V domain can be expressed at the cell surface but prohibits T cell maturation.

Cited by 26 publications

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CD3 components at the surface of pro‐T cells can mediate pre‐T cell development in vivo

CD3 components at the surface of pro‐T cells can mediate pre‐T cell development in vivo

αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain

T cell development in mice lacking the CD3-zeta/eta gene.

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