Positive and Negative Thymocyte Selection Induced by Different Concentrations of a Single Peptide

• Published in: Science (American Association for the Advancement of Science) 1994-03, Vol.263 (5153), p.1615-1618
• Main Authors: Sebzda, Eric, Wallace, Valerie A., Mayer, John, Rae S. M. Yeung, Mak, Tak W., Ohashi, Pamela S.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antigen receptors, T cell; Antigens; Biological and medical sciences; CD4 Antigens - analysis; CD8 Antigens - analysis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; H-2 Antigens; Immunobiology; Lymphocyte Activation; Lymphocytic choriomeningitis virus; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Transgenic; Molecular Sequence Data; Molecules; Negative selection; Neurons; Organ Culture Techniques; Peptide Fragments - immunology; Peptides; Physiological aspects; Positive selection; Receptors; Receptors, Antigen, T-Cell - immunology; T cell antigen receptors; T cells; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymocytes; Thymus Gland - embryology; Thymus Gland - immunology; Transgenic animals; Viral Proteins - immunology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8128249

T lymphocyte maturation is dependent on interactions between the T cell receptor (TCR) expressed on the developing thymocyte and intrathymic major histocompatibility complex (MHC)-peptide ligands. The relation between the peptide-MHC complex that results in negative or positive selection has not been identified. Here, the requirements for the maturation of thymocytes expressing a defined transgenic TCR specific for a viral peptide are studied in fetal thymic organ culture. Low concentrations of the viral peptide antigen recognized by this transgenic TCR can mediate positive selection, whereas high concentrations result in thymocyte tolerance. These findings support the affinity-avidity model of thymocyte selection.