Mapping functional epitopes of the human LFA-1 glycoprotein: monoclonal antibody inhibition of NK and CTL effectors

Hum Immunol. 1986 Nov;17(3):288-96. doi: 10.1016/0198-8859(86)90280-6.

Abstract

Anti-LFA-1 monoclonal antibody (MoAb) was originally identified by screening antibodies for their ability to inhibit cytolysis in the absence of complement. Anti-LFA-1 MoAb has been shown to inhibit both natural killer (NK) and cytolytic T lymphocyte (CTL) mediated cytolysis. To further define the utilization of this molecule in cell-mediated cytolysis, we used a panel of MoAb to functional epitopes on both the alpha and beta chains of the LFA-1 heterodimer. The panel was used to compare OKT3- NK effectors and OKT3+ CTL clones. As expected, function-associated MoAb to CTL antigens (T3, T8, LFA-2) and target cell antigens (HLA, LFA-3) blocked only CTL clones and not NK effectors. In contrast, anti-LFA-1 MoAb blocked both NK effectors and CTL clones. In addition, the panel of anti-LFA-1 MoAb demonstrated an identical hierarchy of functionally relevant LFA-1 epitopes. Given the similar utilization of LFA-1 in NK and CTL mediated cytotoxicity assays, we explored the ability of MoAb to different epitopes on LFA-1 to inhibit conjugate formation. Anti-LFA-1 MoAb inhibition of NK-target binding paralleled the inhibition of CTL-target binding. Thus, functional epitopes on the LFA-1 molecule have been defined for NK and CTL effectors. The identical hierarchy of functional epitopes indicates that the LFA-1 molecule is similarly utilized in NK and CTL mediated cytotoxicity and that the relevant epitopes are involved in effector-target conjugate formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Surface / antagonists & inhibitors
  • Antigens, Surface / immunology*
  • Cell Communication / drug effects
  • Cytotoxicity Tests, Immunologic
  • Epitopes / analysis*
  • Humans
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Leukemia, Experimental / immunology
  • Leukemia, Myeloid / immunology
  • Lymphocyte Function-Associated Antigen-1
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Epitopes
  • Lymphocyte Function-Associated Antigen-1