Synergistic T cell activation via the physiological ligands for CD2 and the T cell receptor

J Exp Med. 1988 Sep 1;168(3):1145-56. doi: 10.1084/jem.168.3.1145.


T cells may be activated either by the antigen-specific T cell receptor (TCR)-CD3 complex or the cell surface receptor CD2. A natural ligand for CD2 has been found to be lymphocyte function-associated antigen 3 (LFA-3), a widely distributed cell surface glycoprotein. To investigate the interaction of these two pathways, we have expressed the cDNA encoding the human CD2 molecule in a murine T cell hybridoma that produces IL-2 in response to HLA-DR antigens. Expression of the CD2 molecule markedly enhances IL-2 production in response to LFA-3+ antigen-bearing stimulator cells, and this stimulation is inhibited by anti-CD2 and anti-LFA-3 mAb. To further define the role of LFA-3 in antigen-dependent T cell activation, we have studied the ability of the purified ligands of CD2 and the TCR to stimulate the hybridoma. Neither liposomes containing purified HLA-DR antigens nor liposomes containing purified LFA-3 were able to stimulate the parent or the CD2+ hybridoma. However, liposomes containing both purified LFA-3 and HLA-DR, the physiological ligands for CD2 and the TCR, respectively, stimulate IL-2 production by the CD2+ but not the parent hybridoma, suggesting that complementary interactions between the TCR-CD3 complex and the CD2 pathway may regulate lymphocyte activation. To determine whether the CD2/LFA-3 interaction participates in cell-cell adhesion and provides an activation signal, we have constructed a cytoplasmic deletion mutant of CD2, CD2 delta B, in which the COOH-terminal 100 amino acids of CD2 have been replaced with a serine. Hybridomas expressing the CD2 delta B molecule were examined. Deletion of the cytoplasmic domain of CD2 did not alter binding of LFA-3 but eliminated the ability of CD2 to increase the response of the hybridoma to liposomes containing both HLA-DR and LFA-3, demonstrating that adhesion of LFA-3 to CD2 alone was insufficient for activation, and that the cytoplasmic domain was required for LFA-3 stimulation through the CD2 molecule. T cells may be activated by purified LFA-3 binding to CD2 and the TCR interacting with its ligand, and these signals appear to be synergistic for the T cell. These results suggest that the CD2/LFA-3 interaction not only plays a role in cell-cell adhesion but provides a stimulatory signal for T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • Antigens, Surface / physiology*
  • CD2 Antigens
  • CD58 Antigens
  • Cell Adhesion
  • DNA Mutational Analysis
  • Humans
  • Hybridomas
  • Interleukin-2 / biosynthesis
  • Ligands
  • Liposomes
  • Lymphocyte Activation*
  • Membrane Glycoproteins / physiology*
  • Mice
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / physiology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • T-Lymphocytes / physiology*
  • Transfection


  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • CD2 Antigens
  • CD58 Antigens
  • Interleukin-2
  • Ligands
  • Liposomes
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic