English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Synthetic bacterial lipopeptide analogs facilitate naive CD4+ T cell differentiation and enhance antigen-specific HLA-II-restricted responses

MPS-Authors
/persons/resource/persons191321

Simon,  Markus M.
Metchnikoff Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Ghielmatti, M., Zwicker, M., Ghielmetti, T., Simon, M. M., Villiger, P. M., & Padovan, E. (2005). Synthetic bacterial lipopeptide analogs facilitate naive CD4+ T cell differentiation and enhance antigen-specific HLA-II-restricted responses. European Journal of Immunology, 35, 2434-2442.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-9345-F
Abstract
Synthetic di- and tri-palmitoylated bacterial lipopeptide analogs (BLpA) can enhance HLA-I-restricted immune responses. Here we show that BLpA indirectly promote antigen-driven differentiation of naive CD4+ T lymphocytes in vitro, with mechanisms that require DC and are inhibited by CTLA-4/Ig. In mixed cultures of cord blood-derived PBMC and allogeneic DC, P3CSK4 lipopeptide facilitated the transition from CCR7+/CD45RA+/CD62L+ to CCR7-/CD45RA-/CD62Ldim T cells with kinetics significantly exceeding those obtained with the unlipidated CSK4 analog. Moreover, P3CSK4 and P2CSK4, but neither the mono-palmitoylated PCSK4 analog nor the CSK4 peptide, increased the frequency of IFN-γ-producing T cells expanded under similar conditions. Along with this, P2CSK4 and P3CSK4, but not PCSK4, restored the in vitro antigenicity of lipoprotein A, and enhanced the frequency of in vitro expanded T cells specific for the tetanus toxoid (TT) and hepatitis B surface antigen (HBsAg) peptides TT947-967 and HBsAg19-33 and for TT. Altogether, BLpA bearing at least two ester-bonded palmitoyl side chains indirectly enhance antigen-driven CD4+ T cell differentiation. BLpA adjuvanticity is independent of covalent bonding to Ag and Ag formulation. This information may be helpful to generate more potent recombinant vaccines.