Abstract
CD8+ T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8+ T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8+ T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8+ T-cells are relatively CD8-independent. These generic differences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-specific TCRs according to the monomeric interaction affinity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, “blocking” anti-CD8 antibodies can suppress autoreactive CD8+ T-cell activation in a relatively selective manner. These findings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8+ T-cell compartment.
Original language | English |
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Article number | 35332 |
Number of pages | 14 |
Journal | Scientific Reports |
Volume | 6 |
DOIs | |
Publication status | Published - 17 Oct 2016 |
Keywords
- Autoimmunity
- CD8 T-cells
- novel therapy
- type 1 diabetes
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Professor Linda Wooldridge
- Bristol Veterinary School - Chair in Translational Immunology
- Infection and Immunity
- Cancer
Person: Academic , Member