| Author/Editor | Ghielmetti, Mascia; Zwicker, Marianne; Ghielmetti, Tanja; Simon, Markus M; Villiger, Peter M; Padovan, Elisabetta | |
| Title | Synthetic bacterial lipopeptide analogs facilitate naive CD4+ T cell differentiation and enhance antigen-specific HLA-II-restricted responses | |
| Type | članek | |
| Source | Eur J Immunol | |
| Vol. and No. | Letnik 35, št. 8 | |
| Publication year | 2005 | |
| Volume | str. 2434-42 | |
| Language | eng | |
| 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, P3CSI` and PzCSIC4, but neither the mono-palmitoylated PCSI` analog nor the CSIČ4 peptide, increased the frequency of IFN-gama-producing T cells expanded under similar conditions. Along with this, PZCSIC4 and P3CSK4, but not PCSIC4, restored the in vitro antigenicity of MDP-OspA, a non-immunogenic analog of Borrelia burgdorferi major outer surface 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. | |
| Descriptors | ADJUVANTS, IMMUNOLOGIC CD4-POSITIVE T-LYMPHOCYTES CELL DIFFERENTIATION EPITOPES, T-LYMPHOCYTE HISTOCOMPATIBILITY ANTIGENS CLASS II ANTIGEN-PRESENTING CELLS ANTIGENS, DIFFERENTIATION CELLS, CULTURED G0 PHASE IMMUNOGLOBULINS KINETICS LIPOPROTEINS PEPTIDES |