Expression of Ly49A on T cells alters the threshold for T cell responses

• Published in: European journal of immunology 2000-10, Vol.30 (10), p.2849-2856
• Main Authors: Öberg, Linda, Eriksson, Mikael, Fahlén, Linda, Sentman, Charles L.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Ly; Antigens, Viral - immunology; Crosses, Genetic; Cytotoxic T lymphocyte; Cytotoxicity, Immunologic; H-2 Antigens - immunology; histocompatibility antigen H-2; Histocompatibility Antigen H-2D; Lectins, C-Type; Ly-49A antigen; Ly49A; Lymphocyte Activation; Lymphocytic choriomeningitis virus; Lymphocytic choriomeningitis virus - immunology; Lymphoma, T-Cell - pathology; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; NK cell; NK Cell Lectin-Like Receptor Subfamily A; Peptide Fragments - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; Receptors, NK Cell Lectin-Like; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transgenic; Tumor Cells, Cultured
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200010)30:10<2849::AID-IMMU2849>3.0.CO;2-6

In this study we investigated the balance between activating and inhibitory signals during T cell activation. We have used transgenic mice in which CD8+ T cells expressed an inhibitory receptor, Ly49A, and a specific activating α β TCR. This TCR recognizes an lymphocytic choriomeningitis virus peptide in combination with H‐2Db. We observed a quantitative influence on cellular responses that depended upon the activating signals received through the TCR and the inhibitory signals received through Ly49A. By varying the peptide concentration given to stimulating cells or target cells, we could adjust the amount of ligand available to trigger the TCR. At low doses of peptide, Ly49A‐expressing T cells were unresponsive on target cells that expressed H‐2Dd, but responded against target cells without H‐2Dd. However, this inhibition could be overcome by increasing the peptide concentration or by addition of anti‐Ly49A F(ab')2 fragments. Thus, rather than behaving as simple "off" switches, our data indicate that Ly49 receptors modulate T cell signaling so that higher amounts of activating signals are required for effector‐cell responses.