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

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 c...

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Bibliographic Details
Main Authors: Knobloch, Martina (Author) , Schönrich, Günther (Author) , Schenkel, Johannes (Author) , Hämmerling, Günter J. (Author) , Arnold, Bernd (Author)
Format: Article (Journal)
Language:English
Published: 01 October 1992
In: International immunology
Year: 1992, Volume: 4, Issue: 10, Pages: 1169-1174
ISSN:1460-2377
DOI:10.1093/intimm/4.10.1169
Online Access:Verlag, Volltext: http://dx.doi.org/10.1093/intimm/4.10.1169
Verlag, Volltext: https://academic.oup.com/intimm/article/4/10/1169/659920
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Author Notes:Martina Knobloch, Günther Schönrich, Johannes Schenkel, Marie Malissen, Bernard Malissen, Anne-Marie Schmitt-Verhulst, Günter J. Hämmerling, and Bernd Arnold
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Summary: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.
Item Description:Gesehen am 21.02.2019
Physical Description:Online Resource
ISSN:1460-2377
DOI:10.1093/intimm/4.10.1169

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