Abstract
We have examined binding characteristics for a single TCR interacting with five of its different peptide/MHC ligands using surface plasmon resonance. We find that very small structural changes produce ligands with similar equilibrium binding affinities (K(D)) for the TCR, but vastly different potencies for T cell activation. Ligands with similar K(D)s induce similar amounts of total phospho-zeta but distinct patterns of zeta phosphorylation. Lower potency ligands induce only incomplete phosphorylation of TCR zeta and generally have faster off-rates. Therefore, the potency of TCR ligands is primarily determined by the half-life of the TCR-ligand complex and the consequent ability to induce complete phosphorylation of zeta.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Hemoglobins / agonists
-
Hemoglobins / antagonists & inhibitors
-
Hemoglobins / genetics
-
Hemoglobins / metabolism*
-
Histocompatibility Antigens Class II / metabolism*
-
Kinetics
-
Ligands
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Mice
-
Peptide Fragments / agonists
-
Peptide Fragments / antagonists & inhibitors
-
Peptide Fragments / genetics
-
Peptide Fragments / metabolism*
-
Phosphorylation
-
Protein Binding
-
Receptors, Antigen, T-Cell / genetics
-
Receptors, Antigen, T-Cell / metabolism*
-
Signal Transduction*
-
Solubility
Substances
-
Hemoglobins
-
Histocompatibility Antigens Class II
-
I-E-antigen
-
Ligands
-
Membrane Proteins
-
Peptide Fragments
-
Receptors, Antigen, T-Cell
-
antigen T cell receptor, zeta chain
-
hemoglobin (64-76)