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CD8+ T cells maintain tolerance to myelin basic protein by 'epitope theft'
Antoine Perchellet1, Ingunn Stromnes, Jennifer M Pang
1Department of Immunology, University of Washington, Box 357650, Seattle, Washington 98195, USA.
Nature Immunology
|May 18, 2004
Summary
Mechanisms of immune tolerance were studied using myelin basic protein (MBP)-specific CD8(+) T cells. Higher-affinity T cells prevented tolerance of lower-affinity cells, revealing a novel immune regulation strategy.
Area of Science:
- Immunology
- Neuroscience
- Autoimmunity
Background:
- CD8(+) T cells targeting myelin basic protein (MBP) can trigger central nervous system (CNS) autoimmunity.
- Immune tolerance normally prevents these autoreactive T cells from causing disease.
Purpose of the Study:
- To define the mechanisms underlying immune tolerance to MBP-specific CD8(+) T cells.
- To investigate the role of T cell receptor (TCR) affinity in tolerance induction.
Main Methods:
- Development of two T cell receptor-transgenic mouse lines with varying affinities for the H-2K(k)-restricted MBP(79-87) epitope.
- Analysis of thymic deletion and peripheral tolerance induction in response to the MBP epitope.
Main Results:
- Lower-affinity MBP-specific T cells exhibited both thymic deletion and peripheral tolerance.
- Higher-affinity T cells did not undergo tolerance induction.
- Higher-affinity T cells suppressed tolerance of lower-affinity T cells by removing H-2K(k)-MBP(79-87) complexes from antigen-presenting cells without proliferation.
Conclusions:
- Immune tolerance mechanisms can be influenced by T cell receptor affinity.
- A novel form of immune regulation exists where high-affinity autoreactive T cells can inhibit tolerance induction in lower-affinity counterparts.
- This regulatory mechanism may limit responses of self-reactive T cells that evade other tolerance pathways.