CD3η and CD3ζ are alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development

The CD3η subunit of the T-cell receptor is thought to subserve an important role in signal transduction and possibly T-cell development. Herein we characterize the organization of the mouse CD3η gene and show that it is part of one gene locus that also encodes CD3ζon chromosome 1. The NH₂-terminal sequence of CD3ζ and CD3η, which share the same leader peptide and are identical through amino acid 122 of each mature protein, is encoded by exons 1-7. However, exons 8 and 9 are differentially spliced to give rise to CD3ζ and CD3η: exons 1-8 encode CD3ζ and exons 1-7 plus 9 encode CD3η. RNase protection analysis with RNA from a variety of fetal, neonatal, and adult cell types indicates that expression of both gene products is T-lineage-restricted. Importantly, expression of CD3ζ and CD3η mRNA appears before or on day 16 of fetal gestation. Expression is apparently coordinate since no cell types tested express CD3ζ or CD3η alone. The steady-state level of CD3ζ mRNA is ≥40-60 times that of CD3η mRNA. In immature CD4⁺CD8⁺CD3^low double-positive thymocytes and CD4⁺CD8^-CD3^high or CD4^-CD8⁺CD3^high single-positive thymocytes, the respective steady-state CD3ζ and CD3η mRNA levels are equivalent, whereas the amount of receptor-associated CD3ζ and CD3η proteins in double-positive thymocytes is ≈10 times less than in single-positive thymocytes. Nevertheless, the CD3ζ/CD3η protein ratio remains constant in all populations (40-60:1). Furthermore, discordance between mRNA and protein levels for CD3ζ and CD3η is also observed in splenic T cells. Thus, post-transcriptional and/or transcriptional regulatory mechanisms control CD3ζ and CD3η expression during T-cell development.