TCR affinity promotes CD8+ T cell expansion by regulating survival

M Hommel, PD Hodgkin - The Journal of Immunology, 2007 - journals.aai.org
M Hommel, PD Hodgkin
The Journal of Immunology, 2007journals.aai.org
Ligation with high affinity ligands are known to induce T lymphocytes to become fully
activated effector cells while ligation with low affinity ligands (or partial agonists) may result
in a delayed or incomplete response. We have examined the quantitative features of CD8+ T
cell proliferation induced by peptides of different TCR affinities at a range of concentrations
in the mouse OT-I model. Both the frequency of cells responding and the average time taken
for cells to reach their first division are affected by peptide concentration and affinity …
Abstract
Ligation with high affinity ligands are known to induce T lymphocytes to become fully activated effector cells while ligation with low affinity ligands (or partial agonists) may result in a delayed or incomplete response. We have examined the quantitative features of CD8+ T cell proliferation induced by peptides of different TCR affinities at a range of concentrations in the mouse OT-I model. Both the frequency of cells responding and the average time taken for cells to reach their first division are affected by peptide concentration and affinity. Consecutive division times, however, remained largely unaffected by these variables. Importantly, we identified affinity to be the sole regulator of cell death in subsequent division. These results suggest a mechanism whereby TCR affinity detection can modulate the subsequent rate of T cell growth and ensure the dominance of higher affinity clones over time.
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