The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal

J Mol Cell Immunol. 1986;2(4):179-90.


The T cell surface molecules Lyt-2 and L3T4 are strongly correlated with the class of MHC gene product recognized by the T cell bearing them. The L3T4 molecule has been proposed to play a role in enhancing recognition of antigen:Ia by specific T cells. In the present experiments, we have explored the role of L3T4 in T cell activation by examining the effects of the L3T4-specific monoclonal antibody GK1.5 on T cell responses in the presence or absence of class II-MHC gene products. Our studies show that GK1.5 inhibits T cell activation in the absence of class II-MHC gene products, while antibodies to other T cell surface molecules do not transduce negative signals to the same cells. We interpret our results as suggesting a signaling role for L3T4 and, by inference, for Lyt-2 as well. We would propose that L3T4 molecules on the class II-restricted T cell initiate the interaction between the L3T4+ T cell and its class II-MHC gene product bearing target cell (B cell, APC). This initial contact is important in allowing a finite time for antigen, Ia, and the T cell receptor to form an activating complex, which in turn transduces a dominant on signal to the cell. In the absence of specific antigen, or if the class II-bearing cell is of the wrong MHC genotype, so that the antigen:Ia receptor is not aggregated, then the association of L3T4 with class II molecules transduces a net negative signal to the T cell. We suggest that this negative signal is responsible for T cell:target cell deconjugation under these circumstances. Thus, we would propose that L3T4 initiates T cell:Ia-bearing cell interactions and, a finite time later, signals the T cell to discontinue the interaction unless a stimulating level of the antigen:Ia complexes for which the T cell's receptor is specific is present.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigen-Presenting Cells / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Antigens, Ly / immunology*
  • Calcium / analysis
  • Cell Communication
  • Cytotoxicity, Immunologic
  • Histocompatibility Antigens Class II / immunology*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred Strains
  • Models, Biological
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Immunologic / immunology*
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Ly
  • Histocompatibility Antigens Class II
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Calcium