T cell avidity determines the level of CTL activation.
To investigate the influence of avidity on T cell activation in vitro and in vivo, we analyzed T cells from St40 and St42 mice, which express the same transgenic TCR specific for an E1a-derived epitope of adenovirus type 5 with different expression levels and therefore different avidities. Splenocytes from both strains showed comparable cytolytic activities and required identical peptide concentrations for efficient target cell lysis and up-regulation of activation markers. However, the kinetics of CD25 up-regulation were strikingly different: whereas the majority of the high-avidity St42 T cells up-regulated the IL-2Ralpha chain within a few hours, low-avidity St40 T cells expressed only 50% of the CD25 of high-avidity T cells after 2 days. In addition, low-avidity T cells proliferated poorly and displayed impaired secretion of IL-2 and IFN-gamma. Similar results were seen with high-avidity St42 T cells stimulated with a partial agonistic peptide. Upon adoptive transfer and subsequent immunization with adenovirus, both high- and low-avidity T cells expanded, but St40 T cells were undetectable 10 days after immunization. Our model system now allows analysis of whether T cells with identical specificities but different avidities influence each other during activation and homeostatic proliferation.
Hofmann
Matthias
M
Institute for Cell Biology, Department of Immunology, Eberhard-Karls-University, Tübingen, Germany.
Radsak
Markus
M
Rechtsteiner
Gerd
G
Wiemann
Katrin
K
Günder
Marc
M
Bien-Gräter
Ursula
U
Offringa
Rienk
R
Toes
René E M
RE
Rammensee
Hans-Georg
HG
Schild
Hansjörg
H
D000256:Adenoviridae / Q000502:physiology; D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2