Temperature requirements and kinetics of T cell signaling. Velocity of triggering correlates with functional effects of anti-CD3 mAb

J Immunol. 1989 May 1;142(9):2971-80.

Abstract

Antibody reactive with the CD3 complex on the surface of T lymphocytes can either: inhibit CTL lysis of target cells expressing Ag; or redirect CTL to lyse target cells expressing FcR in the absence of Ag expression. To investigate these phenomena we examined the effect of anti-CD3 mAb on two indicators of CTL activation, the release of esterase and target cell lysis. Esterase release by long term allo-reactive human CTL in response to target cells (JY or HLA transfected K562 cells) was found to be Ag specific and correlate with target cell lysis. Addition of anti-CD3 to either JY targets or K562 cells expressing FcR resulted in a high level of esterase release. Triggering of esterase release was found with both soluble intact and Fab fragment of anti-CD3 in the absence of cells expressing measurable FcR. This apparent FcR-independent triggering of esterase release occurred at 37 degrees C but not at 24 degrees C. In contrast esterase activity was released from CTL at both 24 and 37 degrees C in response to intact target cells, JY or K562 cells plus intact anti-CD3 mAb. Addition of anti-CD3 mAb, at a level capable of blocking target cell lysis by greater than 50%, resulted in an initial velocity of esterase release almost twice that found in response to JY target cells. With a low level of anti-CD3 mAb, able to block JY lysis by approximately 10%, the initial rate of esterase release was much slower than that found in response to target cells. In contrast when FcR+ cells, K562, were added along with a low level of anti-CD3 the initial velocity of esterase release was about twofold more than the velocity of esterase release triggered by soluble anti-CD3 alone. These results indicate that soluble antibody can trigger long term active CTL and the velocity of this triggering correlates with anti-CD3-mediated inhibition as well as redirected lysis.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / physiology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD3 Complex
  • Cell Line
  • Cytotoxicity, Immunologic*
  • Epitopes / analysis
  • Esterases / metabolism
  • Humans
  • Immunoglobulin Fab Fragments / physiology
  • Kinetics
  • Lymphocyte Activation*
  • Muromonab-CD3
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Fc / physiology
  • T-Lymphocytes, Cytotoxic / enzymology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Temperature*

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Epitopes
  • Immunoglobulin Fab Fragments
  • Muromonab-CD3
  • Receptors, Antigen, T-Cell
  • Receptors, Fc
  • Esterases
  • serine esterase