Control of antigen presentation with a photoreleasable agonist peptide.
The immunological synapse is a specialized intercellular junction between a T cell and a target cell that orchestrates the engagement of receptors and ligands in space and time as a means of regulating function. Here we introduce a reagent for controlling the spatial and temporal presentation of natural antigen to T cells. Moth cytochrome c (88-103) peptide (MCC), an agonist to the murine T cell receptor AND when presented in the context of H2 IEk major histocompatibility complex (IEk), was synthesized with the side-chain amine of Lys99 conjugated to a photosensitive protecting group, 6-nitroveratryloxycarbonyl (NVOC). Cells plated on supported bilayers displaying mobile intercellular adhesion molecule-1 (ICAM-1) and NVOC-MCC loaded IEk did not form immunological synapses and exhibited low intracellular calcium levels, similar to cells presented with self-peptide. Irradiation with UV light was sufficient to restore agonist activity in situ.
DeMond
Andrew L
AL
Biophysics Graduate Group and Department of Chemistry, University of California, Berkeley, California 94720, USA.
Starr
Toby
T
Dustin
Michael L
ML
Groves
Jay T
JT
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D020013:Calcium Signaling; D008051:Lipid Bilayers; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D010777:Photochemistry; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D014466:Ultraviolet Rays
D008051:Lipid Bilayers; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell