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

Three major alternative hypotheses have been pro- † Lymphocyte Biology Section posed as explanations, the "cosignal/unique peptide," Laboratory of Immunology "quantitative threshold or avidity," and "quality of signal" National Institute of Allergy and Infectious Diseases models. The first postulates that thymocytes simultane-National Institutes of Health ously signaled through the TCR and by the CD28 costim-Bethesda, Maryland 20892 ulatory pathway undergo apoptosis. Epithelial thymic stromal cells mediating positive selection differ from the hematopoietic cells typically involved in negative Summary selection in lacking expression of the CD80/CD86 costimulatory molecules (Punt et al., 1994; Amsen and CD4 ؉ CD8 ؉ thymocyte differentiation requires TCR sig-Kruisbeek, 1996; Kishimoto et al., 1996; Lesage et al., naling induced by self-peptide/MHC ligands. Never-1997). Only thymocytes with TCR recognizing peptide/ theless, the resulting mature T cells are not activated MHC complexes uniquely expressed on the costimulaby these self-complexes, whereas foreign ligands can tory-deficient stromal cells (Nakagawa et al., 1998) are be potent stimuli. Here, we show that the signaling presumed to survive the selection process, preventing properties of TCR change during thymocyte maturaexport