Differing roles for B7 and intercellular adhesion molecule-1 in negative selection of thymocytes
| Autor: | Per A. Peterson, Anders Brunmark, Hidehiro Kishimoto, Jonathan Sprent, Zeling Cai, M R Jackson |
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| Rok vydání: | 1996 |
| Předmět: |
Receptors
Antigen T-Cell alpha-beta Transgene Molecular Sequence Data Immunology Intercellular Adhesion Molecule-1 Antigen-Presenting Cells Apoptosis Mice Transgenic Thymus Gland Major histocompatibility complex Mice Negative selection T-Lymphocyte Subsets MHC class I Cell Adhesion Animals Immunology and Allergy Amino Acid Sequence Cell adhesion Antigen-presenting cell biology T-cell receptor Articles Molecular biology Drosophila melanogaster B7-1 Antigen biology.protein Peptides |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | To ensure self tolerance, immature thymocytes with high binding affinity for self peptides linked to major histocompatibility complex (MHC) molecules are eliminated in situ via apoptosis (negative selection). The roles of two costimulatory molecules, B7-1 and intercellular adhesion molecule-1 (ICAM-1), in negative selection was examined by studying apoptosis of T cell receptor transgenic CD4+8+ thymocytes cultured with specific peptides presented by MHC class I-transfected Drosophila cells. When coexpressed on these cells, B7-1 and ICAM-1 act synergistically and cause strong class 1-restricted negative selection of thymocytes. When expressed separately, however, B7-1 and ICAM-1 display opposite functions: negative selection is augmented by B7-1, but is inhibited by ICAM-1. It is notable that B7-1 is expressed selectively in the thymic medulla, whereas ICAM-1 is expressed throughout the thymus. Because of this distribution, the differing functions of B7-1 and ICAM-1 may dictate the sites of positive and negative selection. Thus, in the cortex, the presence of ICAM-1, but not B7-1, on the cortical epithelium may preclude or reduce negative selection and thereby promote positive selection. Conversely, the combined expression of B7-1 and ICAM-1 may define the medulla as the principal site of negative selection. |
| Databáze: | OpenAIRE |
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