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

Ghielmatti, Mascia; Zwicker, Marianne; Ghielmetti, Tanja; Simon, Markus M.; Villiger, Peter M.; Padovan, Elisabetta

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

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

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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: https://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^-/CD62L^dim 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 TT_947-967 and HBsAg_19-33 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.