The CD8 coreceptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR) binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~ 1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~ 10-fold). In this study, we used a panel of MHCI mutants with altered CD8 binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity.
- CD8 coreceptor
- T-cell activation
- T-cell biology
- T-cell receptor (TCR)
- T-cell specificity
- T-cell therapy
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- Bristol Veterinary School - Professor of Comparative Immunology
- Infection and Immunity (Including Veterinary Public Health and Meat Quality)
- Biostatistics, Epidemiology, Mathematics and Ecology
- Cabot Institute for the Environment
- Infection and Immunity
Person: Academic , Member