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

Abstract

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.