CD3-ETA AND CD3-ZETA ARE ALTERNATIVELY SPLICED PRODUCTS OF A COMMON GENETIC-LOCUS AND ARE TRANSCRIPTIONALLY AND OR POSTTRANSCRIPTIONALLY REGULATED DURING T-CELL DEVELOPMENT

The CD3-eta 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 CD3-eta gene and show that it is part of one gene locus that also encodes CD3-zeta on chromosome 1. The NH2-terminal sequence of CD3-zeta and CD3-eta, 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 CD3-zeta and CD3-eta: exons 1-8 encode CD3-zeta and exons 1-7 plus 9 encode CD3-eta. 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 CD3-zeta and CD3-eta mRNA appears before or on day 16 of fetal gestation. Expression is apparently coordinate since no cell types tested express CD3-zeta or CD3-eta alone. The steady-state level of CD3-zeta mRNA is greater-than-or-equal-to 40-60 times that of CD3-eta mRNA. In immature CD4+CD8+CD3low double-positive thymocytes and CD4+CD8-CD3high or CD4-CD8+ CD3 high single-positive thymocytes, the respective steady-state CD3-zeta and CD3-eta mRNA levels are equivalent, whereas the amount of receptor-associated CD3-zeta and CD3-eta proteins in double-positive thymocytes is almost-equal-to 10 times less than in single-positive thymocytes. Nevertheless, the CD3-zeta/CD3-eta protein ratio remains constant in all populations (40-60:1). Furthermore, discordance between mRNA and protein levels for CD3-zeta and CD3-eta is also observed in splenic T cells. Thus, post-transcriptional and/or transcriptional regulatory mechanisms control CD3-zeta and CD3-eta expression during T-cell development.