Clement, Mathew  ORCID: https://orcid.org/0000-0002-9280-5281, Pearson, James ORCID: https://orcid.org/0000-0002-2867-2269, Gras, Stephanie, Van den berg, Hugo, Lissina, Anya, Llewellyn-Lacey, Sian, Willis, Mark ORCID: https://orcid.org/0000-0003-3024-6063, Dockree, Tamsin, McLaren, James ORCID: https://orcid.org/0000-0002-7021-5934, Ekeruche-Makinde, Julia, Gostick, Emma, Robertson, Neil ORCID: https://orcid.org/0000-0002-5409-4909, Burrows, Scott, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845, Peakman, Mark, Skowera, Ania and Wooldridge, Linda
2016.
Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies.
Scientific Reports
6
, 35332.
10.1038/srep35332
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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 speci city 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-speci c CD8+ T-cells are relatively CD8-independent. These generic di erences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-speci c TCRs according to the monomeric interaction a nity 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 ndings 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.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General) |
| Additional Information: | This work is licensed under a Creative Commons Attribution 4.0 International License. |
| Publisher: | Nature Publishing Group |
| ISSN: | 2045-2322 |
| Funders: | Wellcome Trust |
| Related URLs: | |
| Date of First Compliant Deposit: | 17 October 2016 |
| Date of Acceptance: | 9 September 2016 |
| Last Modified: | 11 Oct 2023 20:34 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/95381 |
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