B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse

Immunity. 2004 Sep;21(3):401-13. doi: 10.1016/j.immuni.2004.06.017.


The reported affinity differences between CD28 and CTLA-4 binding to B7-1 and B7-2 may serve to selectively regulate CD28 and CTLA-4 function by differentially recruiting and/or stabilizing these molecules at the immunological synapse. Here we show that ligand binding is important for the accumulation of both CD28 and CTLA-4 at the synapse. While CD28 is recruited to the synapse in the absence of B7-1 and B7-2 binding, it is not effectively stabilized there, as its localization can be disrupted by CTLA-4. In the case of CTLA-4, ligand binding is critical for its concentration at the synapse. We also demonstrate that the affinity and avidity differences in ligand binding translate into selective recruitment of CD28 or CTLA-4 to the immunological synapse--B7-1 is the major ligand mediating CTLA-4 localization, while B7-2 is the main ligand for CD28 concentration at the synapse.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • Antigens, Differentiation / metabolism
  • B7-1 Antigen / immunology*
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology*
  • CD28 Antigens / metabolism
  • CTLA-4 Antigen
  • Flow Cytometry
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Mutation
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • Cd86 protein, mouse
  • Ctla4 protein, mouse
  • Membrane Glycoproteins