T cell activation and thymic tolerance induction require different adhesion intensities of the CD8 co-receptor

• Verfasst von: Knobloch, Martina [VerfasserIn]
• Verfasst von: Schönrich, Günther [VerfasserIn]
• Verfasst von: Schenkel, Johannes [VerfasserIn]
• Verfasst von: Hämmerling, Günter J. [VerfasserIn]
• Verfasst von: Arnold, Bernd [VerfasserIn]
• Titel: T cell activation and thymic tolerance induction require different adhesion intensities of the CD8 co-receptor
• Verf.angabe: Martina Knobloch, Günther Schönrich, Johannes Schenkel, Marie Malissen, Bernard Malissen, Anne-Marie Schmitt-Verhulst, Günter J. Hämmerling, and Bernd Arnold
• Umfang: 6 S.
• Fussnoten: Gesehen am 21.02.2019
• Titel Quelle: Enthalten in: International immunology
• Jahr Quelle: 1992
• Band/Heft Quelle: 4(1992), 10, S. 1169-1174
• ISSN Quelle: 1460-2377
• DOI: doi:10.1093/intimm/4.10.1169
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1587860325

Abstract

Activation of mature lymphocytes requires in addition to the TCR contact with the corresponding antigen the binding of the CD8 or CD4 co-receptors to MHC class I or class II proteins respectively. To investigate the contribution of the CD8 - class I interaction to the elimination of autoreactive T cells during negative selection in the thymus we generated two types of transgenic mice. One set expressed a modified Kb molecule which contained a human HLA-A2 α3 domain, thereby missing the binding residues for the murine CD8 molecules. The second set of mice expressed an anti-Kb specific TCR. Both lines were crossed and in the resulting double transgenic mice the development of Kb-reactlve T cells was followed with an anti-clonotyplc antibody. Surprisingly, efficient clonal deletion In the thymus was still observed, although the reduced CD8 - class l adhesion abrogated effector functions in vivo and in vitro. These results imply that even T cells with intermediate affinity for self are negatively selected In the thymus despite the fact that they are not able to react against self antigens in the periphery. Thus a safety window is created which decreases the risk of autoaggression.