Negative Selection of CD4+CD8+Thymocytes by T-Cell Receptor Peptide Antagonists

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 9; pp. 4057 - 4061
• Main Authors: Page, Dawne M., Alexander, Jeff, Snoke, Ken, Appella, Ettore, Sette, Alessandro, Hedrick, Stephen M., Grey, Howard M.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 26.04.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antigens; Base Sequence; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8 Antigens - immunology; Clonal Deletion; Cultured cells; Cytochromes; Fibroblasts; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunity (Disease); Immunobiology; Lymph nodes; Lymphocyte Activation; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Medical research; Mice; Mice, Transgenic; Molecular Sequence Data; Molecules; Negative selection; Peptides - chemistry; Peptides - immunology; Receptors, Antigen, T-Cell - physiology; T cell antigen receptors; T lymphocytes; T-Lymphocyte Subsets - immunology; Thymocytes; Thymus Gland - cytology; T cell receptor; Peptides; Thymocyte; Selection; Rodentia; Transgenic animal; In vitro; Mechanism; Vertebrata; Mammalia; Mouse; T-Lymphocyte; Antagonist
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.9.4057

Antigen-induced activation of T cells can be specifically inhibited by antigen analogs that have been termed T-cell receptor peptide antagonists. These antagonists appear to act by inducing the formation of nonstimulatory or partially stimulatory complexes between T-cell receptors and the major histocompatibility complex molecules presenting the peptides. Herein, we have investigated the effect of T-cell receptor peptide antagonists on thymocyte negative selection. First, peptide antagonists were identified for the cytochrome c-specific T-cell clone AD10. These peptides were then tested for their ability to induce negative selection in an in vitro model system using thymocytes from mice transgenic for the AD10 T-cell receptor. Though unable to induce mature T-cell activation, the T-cell receptor peptide antagonists induced deletion of CD4+CD8+thymocytes. These results suggest that negative selection of CD4+CD8+thymocytes can be induced by T-cell receptor interactions of a lower affinity than those required for mature T-cell activation.