Complete but curtailed T-cell response to very low-affinity antigen

Nature. 2009 Mar 12;458(7235):211-4. doi: 10.1038/nature07657. Epub 2009 Jan 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Affinity / immunology*
  • Antigens, Bacterial / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Movement / immunology
  • Immunologic Memory / immunology
  • Ligands
  • Listeria monocytogenes / immunology
  • Listeriosis / immunology
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology*


  • Antigens, Bacterial
  • Ligands