Complete but curtailed T-cell response to very low-affinity antigen.
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.
Zehn
Dietmar
D
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, Washington 98195, USA.
Lee
Sarah Y
SY
Bevan
Michael J
MJ
D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D008024:Ligands; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D008024:Ligands