Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation

Immunity. 1997 Oct;7(4):549-57. doi: 10.1016/s1074-7613(00)80376-3.


Efficient T cell activation requires the engagement of a variety of ligand/receptor molecules in addition to T cell receptor (TCR)-major histocompatibility complex (MHC)/peptide interactions. The leukocyte function antigen 1 (LFA-1) and the CD28 glycoprotein have both been implicated in T cell activation. The present study dissects the roles of LFA-1 and CD28 in the activation of naive virus-specific CD8+ T cells. We demonstrate that LFA-1 facilitates T cell activation by lowering the amounts of antigen necessary for T cell activation. In the absence of LFA-1, 100-fold more antigen was required for T cell-antigen-presenting cell (APC) conjugation and all subsequent events of T cell activation, including TCR down-regulation, Ca2+-flux, T cell proliferation, and lytic effector cell induction. Thus, LFA-1 facilitates the functional triggering of TCRs by promoting adhesion of T cells to APCs but does not affect T cell activation otherwise. In contrast, CD28 played an entirely different role during T cell activation. CD28 reduced the number of TCRs that had to be triggered for T cell activation and allowed activation of T cells by low affinity ligands. CD28 but not LFA-1 prevented induction of T cell unresponsiveness after stimulation of TCRs. These results demonstrate that LFA-1 and CD28 exhibit distinct, nonoverlapping ways to influence T cell activation and suggest that the terms costimulation and signal 2 should be revisited.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens, Viral / immunology
  • CD28 Antigens / physiology*
  • Calcium / physiology
  • Cell Adhesion
  • Cell Adhesion Molecules / physiology
  • Clonal Anergy
  • Down-Regulation
  • Interleukin-2 / physiology
  • Lymphocyte Activation*
  • Lymphocyte Function-Associated Antigen-1 / physiology*
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Transgenic
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • Antigens, Viral
  • CD28 Antigens
  • Cell Adhesion Molecules
  • Interleukin-2
  • Lymphocyte Function-Associated Antigen-1
  • Peptides
  • Receptors, Antigen, T-Cell
  • Calcium