Publication Date:
2009-02-03
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735344/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735344/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zehn, Dietmar -- Lee, Sarah Y -- Bevan, Michael J -- R01 AI019335/AI/NIAID NIH HHS/ -- R01 AI019335-27/AI/NIAID NIH HHS/ -- R01 AI019335-28/AI/NIAID NIH HHS/ -- R01 AI019335-29/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Mar 12;458(7235):211-4. doi: 10.1038/nature07657. Epub 2009 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19182777" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
