CD3ζ dependence of the CD2 pathway of activation in T lymphocytes and natural killer cells

P. Moingeon, J. L. Lucich, D. J. McConkey, F. Letourneur, B. Malissen, J. Kochan, H. C. Chang, H. R. Rodewald, E. L. Reinherz

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

In T lymphocytes, signal transduction through the CD2 adhesion molecule requires surface expression of the CD3-Ti T-cell receptor (TCR) complex. In contrast, in natural killer (NK) cells, CD2 functions in the absence of a TCR. Because the TCR on T lymphocytes and the CD16 low-affinity IgG Fc receptor (Fcγ receptor type III) complex on NK cells share a common CD3ζ subunit, we reasoned that CD3ζ may be critical for CD2 signaling in T lymphocytes and NK cells. Here we show that transfection of a cDNA encoding a transmembrane form of CD16 into TCR- variants of the Jurkat T-cell line results in CD16 expression in association with endogenous CD3ζ homodimers and restores CD2 signaling function. To test directly the role of CD3ζ in CD2 triggering, we then transfected human CD2 into each of two murine T-T hybridomas that express TCRs containing either a full-length CD3ζ subunit or a truncated CD3ζ subunit incapable of transducing signals. Despite expression of equivalent surface levels of TCR, CD2-mediated signaling is seen only in the T cells containing wild-type CD3ζ. These findings show that (i) CD16 on NK cells is functionally equivalent to the TCR on T lymphocytes for coupling CD2 to signaling pathways and (ii) CD2 signal transduction depends upon the CD3ζ subunit of the TCR complex and, by inference, the CD3ζ subunit of the CD16 complex.

Original languageEnglish (US)
Pages (from-to)1492-1496
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • Ca mobilization
  • accessory molecules
  • interleukin 2 production
  • signal transduction

ASJC Scopus subject areas

  • General

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