Targeted suppression of autoreactive CD8(+) T-cell activation using blocking anti-CD8 antibodies
| Autor: | Mathew Clement, James A. Pearson, Stephanie Gras, Hugo A. van den Berg, Anya Lissina, Sian Llewellyn-Lacey, Mark D. Willis, Tamsin Dockree, James E. McLaren, Julia Ekeruche-Makinde, Emma Gostick, Neil P. Robertson, Jamie Rossjohn, Scott R. Burrows, David A. Price, F. Susan Wong, Mark Peakman, Ania Skowera, Linda Wooldridge |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
STRUCTURAL BASIS
Science & Technology type 1 diabetes CORECEPTOR FUNCTION RECEPTOR RECOGNITION Autoimmunity MULTIPLE-SCLEROSIS KILL BETA-CELLS CD8 T-cells Multidisciplinary Sciences MHC CLASS-I LONG-TERM REMISSION novel therapy CROSS-REACTIVITY Science & Technology - Other Topics COMPLEX CLASS-I CD8+T CELLS |
| Zdroj: | Clement, M, Pearson, J A, Gras, S, van den Berg, H A, Lissina, A, Llewellyn-Lacey, S, Willis, M D, Dockree, T, McLaren, J E, Ekeruche-Makinde, J, Gostick, E, Robertson, N P, Rossjohn, J, Burrows, S R, Price, D A, Wong, F S, Peakman, M, Skowera, A & Wooldridge, L 2016, ' Targeted suppression of autoreactive CD8(+) T-cell activation using blocking anti-CD8 antibodies ', Scientific Reports, vol. 6, 35332 . https://doi.org/10.1038/srep35332 Clement, M, Pearson, J, Gras, S, van den Berg, H A, Lissina, A, Llewellyn-Lacey, S, Willis, M, Dockree, T, McLaren, J E, Ekeruche-Makinde, J, Gostick, E, Robertson, N P, Rossjohn, J, Burrows, S R, Price, D A, Wong, S, Peakman, M, Skowera, A & Wooldridge, L 2016, ' Targeted suppression of autoreactive CD8 + T-cell activation using blocking anti-CD8 antibodies ', Scientific Reports, vol. 6, 35332 . https://doi.org/10.1038/srep35332 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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