Complete but curtailed T cell response to very low affinity antigen

By D. Zehn, Sarah Y. Lee, M. Bevan. Nature, 2009

729 citations recorded by the source corpus.

After an infection, T cells that carry the CD8 marker are activated and undergo a characteristic kinetic sequence of rapid expansion, subsequent contraction and formation of memory cells. The pool of naive T-cell clones is diverse and contains cells bearing T-cell antigen receptors (TCRs) that differ in their affinity for the same antigen. How these differences in affinity affect the function and the response kinetics of individual T-cell clones was previously unknown. Here we show that during the in vivo response to microbial infection, even very weak TCR–ligand interactions are sufficient to activate naive T cells, induce rapid initial proliferation and generate effector and memory cells. The strength of the TCR–ligand interaction critically affects when expansion stops, when the cells exit lymphoid organs and when contraction begins; that is, strongly stimulated T cells contract and exit lymphoid organs later than weakly stimulated cells. Our data challenge the prevailing view that strong TCR ligation is a prerequisite for CD8+ T-cell activation. Instead, very weak interactions are sufficient for activation, but strong TCR ligation is required to sustain T-cell expansion. We propose that in response to microbial challenge, T-cell clones with a broad range of avidities for foreign ligands are initially recruited, and that the pool of T cells subsequently matures in affinity owing to the more prolonged expansion of high-affinity T-cell clones.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/b7270c90062e4fb0f7f7ce9460e9b60de24ed055

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

Amy E. Moran
Keli L. Holzapfel
Yan Xing
Nicole R. Cunningham
K. Hogquist
J. Maltzman
J. Punt
K. Casey

Citations in the corpus

T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse (2011, methodology): “24 h after transfer, mice were infected i.v. with 5 × 103 CFU of L. monocytogenes or variants expressing either the OVAp or one of the OVA altered peptide ligands (Zehn et al., 2009) provided by M. Bevan (University of Washington, Seattle, WA).”