T cell activation by a bispecific anti-CD3/anti-major histocompatibility complex class I antibody

Eur J Immunol. 1990 Jun;20(6):1393-6. doi: 10.1002/eji.1830200627.

Abstract

A bispecific anti-CD3/anti-major histocompatibility complex (MHC) class I antibody (Ab) that is able to activate human T cells in the absence of a second signal has been used to compare activation by this Ab to signaling by anti-CD3 Ab or by antigen (Ag). We have studied early, intermediate and late events that occur after triggering of a tetanus toxoid-specific T cell clone. While bivalent anti-CD3 Ab induce transient (less than 20 min) intracellular Ca2+ concentration increases, the bispecific Ab, like antigen-presenting cells plus Ag, produces sustained (greater than 2 h) elevated intracellular Ca2+ concentration. In addition, while the anti-CD3 Ab only induces low levels of c-myc mRNA lasting less than 3 h, the bispecific Ab induces high levels which are maintained for at least 8 h after triggering. Late events, such as interleukin 2 receptor expression and proliferation, occurring more than 20 h after activation, were seen only when T cells were stimulated by bispecific Ab or by antigen-presenting cell and Ag. Cells activated by linking T cell receptor (TcR)/CD3 to MHC class I antigens could not be activated by cross-linking the MHC and TcR/CD3 structures separately. Therefore, we propose that the bispecific Ab functions by modifying the membrane dynamics of the TcR/CD3 complex, rather than by the generation of a second signal through class I antigens.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / physiology
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD3 Complex
  • Calcium / metabolism
  • Cross-Linking Reagents / pharmacology
  • Gene Expression Regulation / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Lymphocyte Activation / immunology*
  • Mitogens
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins c-myc
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Interleukin-2 / biosynthesis
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Cross-Linking Reagents
  • Histocompatibility Antigens Class I
  • Mitogens
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Calcium