The dependence for leukocyte function-associated antigen-1/ICAM-1 interactions in T cell activation cannot be overcome by expression of high density TCR ligand

J Immunol. 1999 Apr 15;162(8):4399-405.

Abstract

The leukocyte-specific integrin, LFA-1, can enhance T cell activation. However, it is unclear whether the binding of LFA-1 to its ligand, ICAM-1, functions through intercellular adhesion alone, resulting in an augmentation of the TCR signal, or involves an additional LFA-1-mediated cellular signal transduction pathway. We have previously shown that naive CD4+ lymph node T cells, isolated from DO11.10 TCR transgenic mice, are activated by increasing doses of exogenous OVA peptide presented by transfectants expressing both class II and ICAM-1, but not by cells expressing class II alone. To determine whether LFA-1/ICAM-1 interactions were simply enhancing the presentation of low concentrations of specific MHC/peptide complexes generated from exogenously added peptide, we transfected cells with class II that is covalently coupled to peptide, alone or in combination with ICAM-1. These cells express 100-fold more specific class II/peptide complexes than can be loaded onto class II-positive cells at maximum concentrations of exogenous peptide. Despite this high density of TCR ligand, activation of naive CD4+ T cells still requires the coexpression of ICAM-1. LFA-1/ICAM-1 interactions are not required for effective conjugate formation and TCR engagement because presentation of class II/peptide complexes in the absence of ICAM-1 does induce up-regulation of CD25 and CD69. Thus, high numbers of engaged TCR cannot compensate for the lack of LFA-1/ICAM-1 interactions in the activation of naive CD4+ T cells.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Intercellular Adhesion Molecule-1 / physiology*
  • Ligands
  • Lymphocyte Activation*
  • Lymphocyte Function-Associated Antigen-1 / physiology*
  • Mice
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Peptides / genetics
  • Peptides / immunology
  • Peptides / metabolism
  • Receptors, Antigen, T-Cell / biosynthesis*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / immunology
  • Transfection / immunology
  • Tumor Cells, Cultured

Substances

  • Histocompatibility Antigens Class II
  • Ligands
  • Lymphocyte Function-Associated Antigen-1
  • Peptides
  • Receptors, Antigen, T-Cell
  • Intercellular Adhesion Molecule-1
  • Ovalbumin