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

Linda K. Clayton, Luciano D'Adamio, Frank D. Howard, Monica Sieh, Rebecca E. Hussey, Shigeo Koyasu, Ellis L. Reinherz

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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+CD3low double-positive thymocytes and CD4+CD8-CD3high or CD4-CD8+CD3high 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.

Original languageEnglish (US)
Pages (from-to)5202-5206
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number12
StatePublished - Jun 15 1991
Externally publishedYes

Fingerprint

Genetic Loci
Thymocytes
Exons
T-Lymphocytes
Messenger RNA
Proteins
Chromosomes, Human, Pair 1
Ribonucleases
Protein Sorting Signals
T-Cell Antigen Receptor
Genes
Signal Transduction
RNA
Gene Expression
Amino Acids
Pregnancy
Population

Keywords

  • Lymphoid differentiation
  • Signal transduction
  • T-cell receptor
  • Thymic selection

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

CD3η and CD3ζ are alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development. / Clayton, Linda K.; D'Adamio, Luciano; Howard, Frank D.; Sieh, Monica; Hussey, Rebecca E.; Koyasu, Shigeo; Reinherz, Ellis L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 12, 15.06.1991, p. 5202-5206.

Research output: Contribution to journalArticle

Clayton, Linda K. ; D'Adamio, Luciano ; Howard, Frank D. ; Sieh, Monica ; Hussey, Rebecca E. ; Koyasu, Shigeo ; Reinherz, Ellis L. / CD3η and CD3ζ are alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development. In: Proceedings of the National Academy of Sciences of the United States of America. 1991 ; Vol. 88, No. 12. pp. 5202-5206.
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abstract = "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+CD3low double-positive thymocytes and CD4+CD8-CD3high or CD4-CD8+CD3high 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.",
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T1 - CD3η and CD3ζ are alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development

AU - Clayton, Linda K.

AU - D'Adamio, Luciano

AU - Howard, Frank D.

AU - Sieh, Monica

AU - Hussey, Rebecca E.

AU - Koyasu, Shigeo

AU - Reinherz, Ellis L.

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Y1 - 1991/6/15

N2 - 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+CD3low double-positive thymocytes and CD4+CD8-CD3high or CD4-CD8+CD3high 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.

AB - 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+CD3low double-positive thymocytes and CD4+CD8-CD3high or CD4-CD8+CD3high 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.

KW - Lymphoid differentiation

KW - Signal transduction

KW - T-cell receptor

KW - Thymic selection

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