CD2-mediated signaling in T cells lacking the zeta-chain-specific immune receptor tyrosine-based activation (ITAM) motif.
T lymphocytes can be activated via the T cell receptor (TCR) or by triggering through a number of other surface structures, including the CD2 co-receptor molecule. Signaling through the CD2 molecule was shown previously to be dependent on the TCR-associated zeta-chain. Here, we show that CD2-induced activation also functions in T cells which express zeta-chains lacking a functional immune-receptor tyrosine-based activation motif (ITAM). TCR-positive T cells that express only the transmembrane part of the zeta-chain protein and thus lack a functional zeta-derived ITAM readily produce interleukin (IL)-2 when cross-linked with CD2-specific monoclonal antibodies (mAb). TCR-negative T cell hybridomas expressing minimal receptors consisting of an extracellular CD25 and an intracellular zeta-chain-derived segment were effectively stimulated via CD2-specific mAb. For CD2-mediated co-stimulation of TCR-negative cells, two zeta-chain-derived ITAM were sufficient to induce IL-2 when the CD2 molecules were co-cross-linked with the chimeric CD25-zeta molecules. Taken together, our results show that CD2-induced signaling does not necessarily employ the zeta-chain in TCR-positive cells and that CD2-dependent co-stimulation in TCR-negative cells can be mediated via two functional zeta-chain-derived ITAM.
Steeg
C
C
Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.
von Bonin
A
A
Mittrücker
H W
HW
Malissen
B
B
Fleischer
B
B
D000818:Animals; D001665:Binding Sites; D018801:CD2 Antigens / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014443:Tyrosine / Q000502:physiology
D018801:CD2 Antigens; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D014443:Tyrosine