CD3 zeta dependence of the CD2 pathway of activation in T lymphocytes and natural killer cells.
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 (Fc gamma receptor type III) complex on NK cells share a common CD3 zeta subunit, we reasoned that CD3 zeta 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 CD3 zeta homodimers and restores CD2 signaling function. To test directly the role of CD3 zeta in CD2 triggering, we then transfected human CD2 into each of two murine T-T hybridomas that express TCRs containing either a full-length CD3 zeta subunit or a truncated CD3 zeta 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 CD3 zeta. 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 CD3 zeta subunit of the TCR complex and, by inference, the CD3 zeta subunit of the CD16 complex.
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA.
P
P
Moingeon
J L
JL
Lucich
D J
DJ
McConkey
F
F
Letourneur
B
B
Malissen
J
J
Kochan
H C
HC
Chang
H R
HR
Rodewald
E L
EL
Reinherz
D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001483:Base Sequence; D018801:CD2 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D002118:Calcium