The CD3ζ cytoplasmic domain mediates CD2-induced T cell activation

Frank D. Howard, Philippe Moingeon, Ulrich Moebius, David J. McConkey, Booma Yandava, Tiiu E. Gennert, Ellis L. Reinherz

Research output: Contribution to journalArticle

Abstract

CD2-mediated T lymphocyte activation requires surface expression of CD3-Ti, the T cell receptor (TCR) for antigen major histocompatibility complex protein. Given the importance of CD3ζ in TCR signaling, we have directly examined the ability of the CD3ζ cytoplasmic domain to couple CD2 to intracellular signal transduction pathways. A cDNA encoding a chimeric protein consisting of the human CD3ζ cytoplasmic domain (amino acid residues 31-142) fused to the CD8α extracellular and transmembrane domains (amino acid residues 1-187) was transfected into a CD2+CD3CD8 variant of the human T cell line Jurkat. The resulting transfectants expressed the CD8α/CD3ζ chimeric receptor at the cell surface in the absence of other TCR subunits. Stimulation of these transfectants with anti-T112 + anti-T113 monoclonal antibodies (mAbs) initiated both a prompt cytosolic free calcium ([Ca2+]i) rise and protein tyrosine kinase activation. Stimulation with either intact anti-T112 + anti-T113 mAbs or purified F(ab')2 fragments resulted in interleukin 2 (IL-2) secretion. In contrast, control cell lines transfected with a cDNA encoding wild-type CD8α, and thus lacking surface expression of the CDζ cytoplasmic domain, failed to show any [Ca2+]i rise, protein tyrosine kinase activation, or IL-2 secretion after identical stimulation. These data directly establish the CD3ζ cytoplasmic domain as a necessary and sufficient component of the CD3-Ti complex involved in T lymphocyte activation through CD2. Moreover, they show that CD2 signaling can function in the absence of Fc receptors.

Original languageEnglish (US)
Pages (from-to)139-145
Number of pages7
JournalJournal of Experimental Medicine
Volume176
Issue number1
DOIs
StatePublished - Jul 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Howard, F. D., Moingeon, P., Moebius, U., McConkey, D. J., Yandava, B., Gennert, T. E., & Reinherz, E. L. (1992). The CD3ζ cytoplasmic domain mediates CD2-induced T cell activation. Journal of Experimental Medicine, 176(1), 139-145. https://doi.org/10.1084/jem.176.1.139