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

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

doi:10.1002/eji.200526241

Cited by 9 publications

(3 citation statements)

References 29 publications

(75 reference statements)

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“…The lipopeptide enhanced the frequency of in vitro expanded T H cells specific for tetanus toxoid and hepatitis B surface antigen peptides, with the majority of the expanded CD3 + /CD4 + cells being positive for IFNγ. 106 A recent study indicates that the lipopeptides lower the threshold for T H 1 responses by TLR2-dependent secretion of IL-12p70 by DC. 107 mononuclear cells, 165 as well as strongly activating NK cells in an IL-12-dependent manner.…”

Section: Intracellular Tlr3 Activation: Dsrna and Poly (I:c)mentioning

confidence: 99%

Potential adjuvantic properties of innate immune stimuli

et al. 2009

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Just as the prescient comment by Gaston Ramon was relegated to the last footnote of his 1926 paper, 1 so has research on the mechanisms of action of adjuvants, until recently, languished as parenthetical annotations and addenda in the archives of immunology and vaccine development. Ramon defined immunological adjuvants as "substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone." Interestingly enough, he was referring to his empirical findings that the addition of bread crumbs, tapioca, saponin and 'starch oil' to antigenic preparations greatly enhanced antibody responses to diphtheria or tetanus. 2 A year later, the adjuvanticity of aluminum salts (primarily phosphate and hydroxide) was discovered by Glenny and coworkers. 3 In the 83 years that have elapsed, the repertoire of investigational adjuvants has grown to encompass a very wide range of materials, 4 but aluminum salt-based mineral salts (generically, and incorrectly, termed "alum") have remained the only adjuvants currently approved by the FDA. Aluminum salts have enjoyed a good safety record, but they are weak adjuvants for antibody induction and induce a T helper-2 (T H 2)-skewed, rather than a T helper-1 (T H 1) response. 5,6 Furthermore, not only are aluminum salts ineffective at inducing cytotoxic T lymphocyte (CTL) or mucosal IgA antibody responses, but also have a propensity to induce IgE responses, which have been associated with allergic reactions in some subjects. 5,6 Very recent reports implicate the Nalp3 inflammasome, a component of the innate immune response, as the effector limb of alum-associated adjuvanticity. [7][8][9] In 1962, Dresser observed that injection of purified soluble proteins not only failed to stimulate an immune response, but tolerized animals unless a bacterial extract was admixed with the protein immunogen. 10 This led him to redefine adjuvanticity as "a property of a substance which can act as a physiological switch, directing at least some immunologically competent cells to respond by making antibody rather than by becoming immunologically paralyzed by the antigen," 11 confirming Johnson's earlier observations that lipopolysaccharide (LPS) from Gram-negative bacteria exerted potent adjuvant properties, 12 and perhaps paved the way for the subsequent discovery of the wide range of microorganism-derived adjuvants. 13 TLRs are pattern recognition receptors present on diverse cell types that recognize specific molecular patterns present in molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). 14,15 There are 10 TLRs in the human genome;

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Section: Intracellular Tlr3 Activation: Dsrna and Poly (I:c)mentioning

confidence: 99%

Potential adjuvantic properties of innate immune stimuli

et al. 2009

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“…While our finding agreed with numerous previous studies that the HLA-DRB1*07:01 allele is significantly associated with OBI. Five HLA-DRB1*07:01 restricted HBV helper T lymphocyte epitopes, FFLLTRILTIPQSLD [ 26 ], GMLPVCPLIPGSTTTNTG [ 27 ], TSLNFLGGSPVC [ 27 ], TTNTGPCKTCTTPAQG [ 27 ], WASVRFSWLSLLVPF [ 28 ] have been defined and identified in the Immune epitope database and analysis resource (IEDB) online server ( http://www.iedb.org ). The expression and type of HBV related epitopes in OBI have not been reported.…”

Section: Discussionmentioning

confidence: 99%

High resolution HLA-DRB1 analysis and shared molecular amino acid signature of DRβ1 molecules in Occult hepatitis B infection

Wang

Shen

et al. 2022

BMC Immunol

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Aim To investigate the association of human leukocyte antigen (HLA)-DRB1 alleles and the variations of polymorphic amino acid changes in DRβ1 chain in Shaanxi Han population with Occult hepatitis B infection (OBI). Methods High-resolution HLA-DRB1 genotyping was performed in 107 OBI carriers and 280 normal controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. Three-dimensional modeling was performed to explore the effect of the key residues on the HLA-DRB1 molecule. Results Strong susceptible association for allele DRB1*07:01 was observed in OBI carriers. The amino acid variation at HLA-DRβ1 molecule revealed susceptible associations for residues Gln4β, Val57β(P9), Ser60β(P9) and Val78β(P4), the amino acids Arg4β, Asp57β(P9), Tyr60β(P9) and Tyr78β(P4) showed protective associations. Conclusion Alleles DRB1*07:01 showed strong susceptible associations in OBI carriers. The amino acid variations in DRβ molecules revealed significant molecular markers for susceptibility and protection from OBI in Shaanxi Han population.

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“…However, the synthetic triacylated lipopeptide corresponding to the N-terminal sequences of B. burgdorferi outer surface lipoproteins can induce Th1 phenotype development [17]. Furthermore, the lipopeptide N-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-CSKKKK, Pam3CSK4, a synthetic analog of bacterial and mycoplasmal lipoproteins that recognizes the TLR1/2 complex, can enhance functional memory CD8 + T cells [18, 19] and facilitate antigen-driven CD4 + T cell differentiation [20]. A synthetic derivative of the mycoplasma macrophage-activating lipopeptide-2, BPPcysMPEG, is a potent adjuvant for cross-priming against cellular antigens [21].…”

Section: Introductionmentioning

confidence: 99%

A Purified Recombinant Lipopeptide as Adjuvant for Cancer Immunotherapy

Song

Liu

Chen

et al. 2014

BioMed Research International

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Synthetic lipopeptides have been widely used as vaccine adjuvants to enhance immune responses. The present study demonstrated that the tryptic N-terminal fragment of the lipoprotein rlipo-D1E3 (lipo-Nter) induces superior antitumor effects compared to a synthetic lipopeptide. The lipo-Nter was purified and formulated with protein or peptide vaccines to determine if lipo-Nter could be used as a novel adjuvant and could induce antitumor immunity in a cervical cancer model. Purified lipo-Nter activated the maturation of bone marrow-derived dendritic cells (BM-DCs), leading to the secretion of TNF-α through TLR2/6 but not TLR1/2. A recombinant mutant HPV16 E7 (rE7m) protein was mixed with lipo-Nter to immunize the mice; the anti-E7 antibody titers were increased, and the T helper cells were skewed toward the Th1 fate (increased IL-2 and decreased IL-5 secretion). Single-dose injection of rE7m and lipo-Nter inhibited tumor growth, but the injection of rE7m alone did not. Accordingly, lipo-Nter also enhanced the antitumor immunity of the E7-derived peptide but not the synthetic lipopeptide (Pam3CSK4). We demonstrated that the lipo-Nter of a bacterial-derived recombinant lipoprotein is a novel adjuvant that could be used for the development of a new generation of vaccines.

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

Cited by 9 publications

References 29 publications

Potential adjuvantic properties of innate immune stimuli

Potential adjuvantic properties of innate immune stimuli

High resolution HLA-DRB1 analysis and shared molecular amino acid signature of DRβ1 molecules in Occult hepatitis B infection

A Purified Recombinant Lipopeptide as Adjuvant for Cancer Immunotherapy

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