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