CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold.
Immunol Cell Biol
; 95(1): 68-76, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-27670790
ABSTRACT
The CD8 co-receptor 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Antígenos de Histocompatibilidad Clase I
/
Antígenos CD8
/
Linfocitos T CD8-positivos
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article