TY - JOUR
T1 - B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse
AU - Pentcheva-Hoang, Tsvetelina
AU - Egen, Jackson G.
AU - Wojnoonski, Kathleen
AU - Allison, James P.
N1 - Funding Information:
We thank Jessica Shugart and Jamin Willoughby for assistance with the generation of the fluorescent fusions, and Emily Corse, John Engelhardt, P'ng Loke, and Xingxing Zang for helpful suggestions and/or critical reading of the manuscript. This work was supported by the Howard Hughes Medical Institute and National Institutes of Health Grant CA40041 (to J.P.A.). T.P.H. is a fellow of the Cancer Research Institute.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2004.06.017
DO - 10.1016/j.immuni.2004.06.017
M3 - Article
C2 - 15357951
AN - SCOPUS:4444369694
SN - 1074-7613
VL - 21
SP - 401
EP - 413
JO - Immunity
JF - Immunity
IS - 3
ER -