Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand

Abstract

Activation of resting T lymphocytes is initiated by the interaction of cell-surface receptors with their corresponding ligands. In addition to activation through the CD3 (T3)-Ti antigen-receptor complex¹, recent experiments have demonstrated induction of T-cell proliferation through the CD2 (T11) molecule^2–4, traditionally known as the erythrocyte(E)-receptor, through which T cells can bind red blood cells (RBC)^5–7. This 'alternative pathway' of T-cell activation² was observed in vitro in response to combinations of anti-CD2 monoclonal antibodies (mAbs) that bind to distinct epitopes of CD2, such as mAbs against T11₂ plus T11₃ (ref. 2). The physiological importance of this activation pathway can be assessed only by studying the effects of a naturally occurring ligand of CD2 on T-cell activation. We have recently described such a ligand, a glycoprotein of apparent relative molecular mass 42,000 (M_r 42K) that is expressed on all blood cells and some other tissues^9,11. Here we demonstrate that binding of this cell surface molecule, termed T11 target structure or T11TS, to CD2 (T11) induces reactivity in resting T cells to a mitogenic stimulus given by a mAb to the T11₃ determinant or by submitogenic concentrations of anti-T11₂₊₃ mAbs. Thus, one of the signals required for T-cell activation through the alternative pathway is provided by the interaction of CD2 with a naturally occurring complementary cell-surface molecule.