Purified lymphocyte function‐associated antigen‐3 and T11 target structure are active in CD2‐mediated T cell stimulation

In this study we have used cells expressing LFA‐3 or T11TS, the human and sheep forms of the ligand of CD2, as well as the purified LFA‐3 and T11TS molecules themselves to study their effects on T cell activation via the CD2‐mediated “alternative pathway”. Sheep red blood cells, which bind to CD2 via T11TS in E‐rosette formation, and human autologous monocytes, which express the LFA‐3 molecule, both induce proliferation of resting T cells in the presence of per se submitogenic concentrations of anti‐T112 plus anti‐T113 monoclonal antibodies (mAb). This effect is blocked by mAb to LFA‐3, T11TS and CD2 known to inhibit CD2‐ligand interaction. In addition, purified LFA‐3 and T11TS, when added at ng amounts to cultures containing submitogenic concentrations of anti‐T112 + 3 mAb, are also strongly mitogenic for resting human T cells. Thus, both LFA‐3 and T11TS are potent co‐stimulators of the alternative pathway of T cell activation but by themselves do not provide a mitogenic signal. This finding is discussed with regard to a physiological role of CD2‐LFA‐3 interaction in T cell activation.

[1]  Michael Loran Dustin,et al.  Serologic cross-reactivity of T11 target structure and lymphocyte function-associated antigen 3. Evidence for structural homology of the sheep and human ligands of CD2. , 1987, Journal of immunology.

[2]  Michael Loran Dustin,et al.  Deficiency of lymphocyte function-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. Functional correlates and evidence for a phosphatidylinositol membrane anchor , 1987, The Journal of experimental medicine.

[3]  M. Sanders,et al.  Human T cell rosetting is mediated by LFA-3 on autologous erythrocytes. , 1987, Journal of immunology.

[4]  S. Meuer,et al.  Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand , 1987, Nature.

[5]  Michael Loran Dustin,et al.  The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3 , 1987, Nature.

[6]  Michael Loran Dustin,et al.  Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion , 1987, The Journal of experimental medicine.

[7]  Michael Loran Dustin,et al.  Rosetting of activated human T lymphocytes with autologous erythrocytes. Definition of the receptor and ligand molecules as CD2 and lymphocyte function-associated antigen 3 (LFA-3) , 1987, The Journal of experimental medicine.

[8]  W. Fiers,et al.  Recombinant interleukin-2 directly augments the cytotoxicity of human monocytes , 1987, Nature.

[9]  T. Springer,et al.  Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones , 1986, Nature.

[10]  S. Chouaib,et al.  A common pathway for T lymphocyte activation involving both the CD3-Ti complex and CD2 sheep erythrocyte receptor determinants. , 1986, Journal of immunology.

[11]  T. Hünig The ligand of the erythrocyte receptor of T lymphocytes: expression on white blood cells and possible involvement in T cell activation. , 1986, Journal of immunology.

[12]  O. Majdic,et al.  T cell stimulation via the erythrocyte receptor. Synergism between monoclonal antibodies and phorbol myristate acetate without changes of free cytoplasmic Ca++ levels , 1986, The Journal of experimental medicine.

[13]  M. Miyasaka,et al.  T11TS, the cell surface molecule binding to the “erythrocyte receptor” of T lymphocytes: cellular distribution, purification to homogeneity and biochemical properties , 1986, European journal of immunology.

[14]  D. Olive,et al.  Anti‐CD2 (sheep red blood cell receptor) monoclonal antibodies and T cell activation I. Pairs of anti‐T11.1 and T11.2 (CD2 subgroups) are strongly mitogenic for T cells in presence of 12‐O‐tetradecanoylphorbol 13‐acetate , 1986, European journal of immunology.

[15]  P. Brottier,et al.  T cell activation via CD2 [T, gp50] molecules: accessory cells are required to trigger T cell activation via CD2-D66 plus CD2-9.6/T11(1) epitopes. , 1985, Journal of immunology.

[16]  T. Hünig The cell surface molecule recognized by the erythrocyte receptor of T lymphocytes. Identification and partial characterization using a monoclonal antibody , 1985, The Journal of experimental medicine.

[17]  E. Reinherz,et al.  An alternative pathway of T-cell activation: A functional role for the 50 kd T11 sheep erythrocyte receptor protein , 1984, Cell.

[18]  F. Sánchez‐Madrid,et al.  The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: cell surface antigens associated with CTL-target interactions. , 1983, Journal of immunology.

[19]  Elizabeth Simpson,et al.  A rapid method for the isolation of functional thymus‐derived murine lymphocytes , 1973, European journal of immunology.