T cell avidity determines the level of CTL activation

• Published in: European Journal of Immunology Vol. 34; no. 7; pp. 1798 - 1806
• Main Authors: Hofmann, Matthias, Radsak, Markus, Rechtsteiner, Gerd, Wiemann, Katrin, Günder, Marc, Bien‐Gräter, Ursula, Offringa, Rienk, Toes, René E.M., Rammensee, Hans‐Georg, Schild, Hansjörg
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.07.2004
• Subjects: Activation level; Adenoviridae - physiology; Adenovirus; Adoptive Transfer; Affinity; Animals; Avidity; Biomarkers - analysis; Cell Division; Cells, Cultured; Cytokines - secretion; Immunization; Lymphocyte Activation - immunology; Mice; Mice, Transgenic; Receptors, Antigen, T-Cell - metabolism; Receptors, Interleukin-2 - immunology; Spleen - cytology; Spleen - immunology; T cell; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Cytotoxic - secretion
• ISSN: 0014-2980; 1521-4141; 1365-2567
• DOI: 10.1002/eji.200425088

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 specificfor 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 requiredidentical 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 majorityof the high‐avidity St42 T cells up‐regulated the IL‐2Rα 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‐γ. 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 allowsanalysis of whether T cells with identical specificities but different avidities influence each other during activation and homeostatic proliferation.