Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses

J Exp Med. 1993 Jul 1;178(1):211-22. doi: 10.1084/jem.178.1.211.


Accessory cell surface molecules, such as T cell antigen CD2 and its ligand lymphocyte function-associated antigen 3 (LFA-3; CD58), are critical costimulatory pathways for optimal T cell activation in response to antigens. Interaction of CD2 with cell surface LFA-3 not only increases T cell/accessory cell adhesion, but also induces signal transduction events involved in the regulation of T cell responses. In this report, we show that specific interactions of LFA-3 with CD2 can result in T cell unresponsiveness to antigenic or mitogenic stimuli in vitro. By deletion of certain regions of the extracellular domain of LFA-3, we localized the CD2 binding site to the first domain of LFA-3. We then demonstrated that a soluble, purified first domain-LFA-3/IgG1 fusion protein (LFA3TIP) interacts with CD2 and binds to the same CD2 epitope as purified multimeric or cell surface-expressed LFA-3. LFA3TIP inhibits tetanus toxoid, hepatitis B surface antigen, anti-CD3 mAb, Con A, and phytohemagglutinin P-induced T cell proliferation, as well as xenogeneic and allogeneic mixed lymphocyte reactions (MLR). Unlike anti-LFA-3 or anti-CD2 monoclonal antibodies (mAbs) which inhibit T cell responses by blocking LFA-3/CD2 binding, LFA3TIP is capable of rendering T cells unresponsive to antigenic stimuli in situations where T cell activation is independent of CD2/LFA-3 interactions. Furthermore, LFA3TIP, but not blocking anti-CD2 mAbs, is capable of inducing T cell unresponsiveness to secondary stimulation in allogeneic MLR. This inhibition of T cell responses by LFA3TIP occurs through a different mechanism from that of mAbs to LFA-3 or CD2.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • CD2 Antigens
  • CD58 Antigens
  • CHO Cells
  • Cricetinae
  • Epitopes
  • Humans
  • Lymphocyte Activation
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Receptors, Fc / physiology
  • Receptors, Immunologic / physiology*
  • Recombinant Fusion Proteins / pharmacology
  • T-Lymphocytes / immunology*


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD2 Antigens
  • CD58 Antigens
  • Epitopes
  • Membrane Glycoproteins
  • Receptors, Fc
  • Receptors, Immunologic
  • Recombinant Fusion Proteins