A conformationally-biased, response-selective agonist of C5a acts as a molecular adjuvant by modulating antigen processing and presentation activities of human dendritic cells.
Int Immunopharmacol
; 8(6): 819-27, 2008 Jun.
Article
en En
| MEDLINE
| ID: mdl-18442785
ABSTRACT
A partial mechanism by which a conformationally-biased, response-selective agonist of complement component C5a, Tyr-Ser-Phe-Lys-Pro-Met-Pro-Leu-D-Ala-Arg or YSFKPMPLaR (EP54), acts as a molecular adjuvant is presented by showing the manner in which this peptide engages human dendritic cells (DC). Confocal microscopy was used to show that fluorescent-labeled EP54 (0.2 microM) and fluorescent-labeled B and T cell epitopes attached to EP54 (i.e., EP54-containing vaccines, 0.2 microM) were internalized by human DCs well within 30 min of exposure. After 24 h of exposure, EP54 and the B and T cell epitopes of the EP54-containing vaccines (20 microM) were presented on the DC surface in the context of HLA-ABC and HLA-DR determinants. Also, exposure of DCs to EP54 (50 microg/ml) induced the activation of genes specific for the Th1 cytokines IL-6, IL-12, INFgamma, and TNFalpha as well as the Th2 cytokine IL-4. Internalization, HLA expression, and cytokine gene activation were not observed in the presence of the inactive, scrambled EP54 constructs arguing that these effects of EP54 are mediated predominately via C5a receptors on the DC surface.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Células Dendríticas
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Complemento C5a
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Presentación de Antígeno
Límite:
Humans
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos