Specific Requirement for CD3ε in T Cell Development

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-12, Vol.95 (25), p.14909-14914
• Main Authors: DeJarnette, Jan B., Sommers, Connie L., Huang, Kun, Woodside, Kenneth J., Emmons, Rebecca, Katz, Kenneth, Shores, Elizabeth W., Love, Paul E.
• Format: Article
• Language: English
• Subjects: Alleles; Developmental biology; Exons; Genes; Mice; Phenotypes; T cell antigen receptors; T lymphocytes; Thymocytes; Transgenes
• ISSN: 0027-8424
• DOI: 10.1073/pnas.95.25.14909

T cell antigen receptor (TCR) and pre-TCR complexes are composed of clonotypic heterodimers in association with dimers of signal transducing invariant subunits (CD3γ , -δ , -ε , and ζ ). The role of individual invariant subunits in T cell development has been investigated by generating gene-specific mutations in mice. Mutation of CD3γ , -δ , or ζ results in an incomplete block in development, characterized by reduced numbers of mature T cells that express low levels of TCR. In contrast, mature T cells are absent from CD3ε-/-mice, and thymocyte development is arrested at the early CD4-CD8-stage. Although these results suggest that CD3ε is essential for pre-TCR and TCR expression/function, their interpretation is complicated by the fact that expression of the CD3γ and CD3δ genes also is reduced in CD3ε-/-mice. Thus, it is unclear whether the phenotype of CD3ε-/-mice reflects the collective effects of CD3γ , -δ , and -ε deficiency. By removing the selectable marker (PGK-NEO) from the targeted CD3ε gene via Cre/loxP-mediated recombination, we generated mice that lack CD3ε yet retain normal expression of the closely linked CD3γ and CD3δ genes. These (CD3εΔ /Δ) mice exhibited an early arrest in T cell development, similar to that of CD3ε-/-mice. Moreover, the developmental defect could be rescued by expression of a CD3ε transgene. These results identify an essential role for CD3ε in T cell development not shared by the CD3γ , CD3δ , or ζ -family proteins and provide further evidence that PGK-NEO can influence the expression of genes in its proximity.