CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold

Tamsin Dockree, Christopher Holland, Mick Bailey, Linda Wooldridge

Research output: Contribution to journalArticle (Academic Journal)

4 Citations (Scopus)
276 Downloads (Pure)

Abstract

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 CD8T-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.
Original languageEnglish
Pages (from-to)68–76
Number of pages9
JournalImmunology and Cell Biology
Volume95
Issue number1
Early online date8 Nov 2016
DOIs
Publication statusPublished - 10 Jan 2017

Keywords

  • biophysics
  • CD8 coreceptor
  • immunology
  • lymphocyte
  • T-cell
  • T-cell activation
  • T-cell biology
  • T-cell receptor (TCR)
  • T-cell specificity
  • T-cell therapy

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