Divergent Changes in the Sensitivity of Maturing T Cells to Structurally Related Ligands Underlies Formation of a Useful T Cell Repertoire

• Published in: Immunity (Cambridge, Mass.) Vol. 10; no. 3; pp. 367 - 376
• Main Authors: Lucas, Bruno, S̆tefanová, Irena, Yasutomo, Koji, Dautigny, Nicole, Germain, Ronald N
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.1999
• Subjects: Amino Acid Sequence; Animals; Apoptosis - immunology; Cell Differentiation - immunology; Ligands; Mice; Mice, Transgenic; Molecular Sequence Data; Receptors, Antigen, T-Cell - chemistry; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Signal Transduction - immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Thymus Gland - cytology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80036-9

CD4+CD8+ thymocyte differentiation requires TCR signaling induced by self-peptide/MHC ligands. Nevertheless, the resulting mature T cells are not activated by these self-complexes, whereas foreign ligands can be potent stimuli. Here, we show that the signaling properties of TCR change during thymocyte maturation, differentially affecting responses to related peptide/MHC molecule complexes and contributing to this discrimination. Weak agonists for CD4+CD8+ thymocytes lose potency during development, accompanied by a change in TCR-associated phosphorylation from an agonist to a partial agonist/antagonist pattern. In contrast, sensitivity to strong agonists is maintained, along with full signaling. This yields a mature T cell pool highly responsive to foreign antigen while possessing a wide margin of safety against activation by self-ligands.