CD2-mediated signaling in T cells lacking the zeta-chain-specific immune receptor tyrosine-based activation (ITAM) motif

TY - JOUR

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 -