Early biochemical signals arise from low affinity TCR-ligand reactions at the cell-cell interface.
The kinetics of acid release by a mixture of T cells and antigen presenting cells were measured with a microphysiometer during a brief exposure to antigenic peptides. We find that some of the early biochemical events that lead to cellular proliferation cause a specific increase in the rate of acid release. The duration of this increase in acid release reflects the life-time of the peptide-MHC complexes. Peptides that form long-lived complexes produce a response that is stable for more than an hour. Serial TCR engagement is suggested by the observation that the amplitude of this stable response can be rapidly shifted up or down with additional agonist peptide or with antibodies that block T cell receptor binding. Cells briefly exposed to a peptide that forms short-lived peptide-MHC complexes produce a response that decays rapidly as peptide is washed away. A quantitative analysis of the kinetics of this decay in acidification demonstrates that intercellular TCR-ligand reactions are rapid, reversible, and of low apparent affinity with < 20% of peptide-MHC ligand bound to a TCR at any one time. These results demonstrate that the fraction of peptide-MHC ligands bound to TCRs at the cell-cell interface is no higher than anticipated from the affinities observed in solution for isolated TCRs and ligands.
Beeson
C
C
Department of Chemistry, Stanford University, California 94305, USA.
Rabinowitz
J
J
Tate
K
K
Gütgemann
I
I
Chien
Y H
YH
Jones
P P
PP
Davis
M M
MM
McConnell
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D003574:Cytochrome c Group / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors
D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta