Avtor/Urednik		Ghielmetti, Mascia; Zwicker, Marianne; Ghielmetti, Tanja; Simon, Markus M; Villiger, Peter M; Padovan, Elisabetta
Naslov		Synthetic bacterial lipopeptide analogs facilitate naive CD4+ T cell differentiation and enhance antigen-specific HLA-II-restricted responses
Tip		članek
Vir		Eur J Immunol
Vol. in št.		Letnik 35, št. 8
Leto izdaje		2005
Obseg		str. 2434-42
Jezik		eng
Abstrakt		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.
Deskriptorji		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