CD2-mediated signaling in T cells lacking the zeta-chain-specific immune receptor tyrosine-based activation (ITAM) motif
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CD2-mediated signaling in T cells lacking the zeta-chain-specific immune receptor tyrosine-based activation (ITAM) motif. / Steeg, C; von Bonin, A; Mittrücker, H W; Malissen, B; Fleischer, B.
in: EUR J IMMUNOL, Jahrgang 27, Nr. 9, 01.09.1997, S. 2233-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - CD2-mediated signaling in T cells lacking the zeta-chain-specific immune receptor tyrosine-based activation (ITAM) motif
AU - Steeg, C
AU - von Bonin, A
AU - Mittrücker, H W
AU - Malissen, B
AU - Fleischer, B
PY - 1997/9/1
Y1 - 1997/9/1
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens, CD2
KW - Binding Sites
KW - Lymphocyte Activation
KW - Mice
KW - Receptors, Antigen, T-Cell
KW - Recombinant Fusion Proteins
KW - Signal Transduction
KW - T-Lymphocytes
KW - Tyrosine
U2 - 10.1002/eji.1830270917
DO - 10.1002/eji.1830270917
M3 - SCORING: Journal article
C2 - 9341764
VL - 27
SP - 2233
EP - 2238
JO - EUR J IMMUNOL
JF - EUR J IMMUNOL
SN - 0014-2980
IS - 9
ER -