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Structure-function relationships of protein-lipopeptide complexes and influence on immunogenicity.
- Source :
-
Amino acids [Amino Acids] 2017 Oct; Vol. 49 (10), pp. 1691-1704. Date of Electronic Publication: 2017 Jul 17. - Publication Year :
- 2017
-
Abstract
- The lipopeptide, R <subscript>4</subscript> Pam <subscript>2</subscript> Cys, associates electrostatically with soluble protein antigens and significantly enhances their ability to induce protective humoral and cell-mediated responses. We demonstrate that antibody titers elicited by the antigen ovalbumin (OVA) associated with R <subscript>4</subscript> Pam <subscript>2</subscript> Cys are higher than those elicited by OVA in the presence of alum and comparable to those elicited by OVA formulated with complete Freund's adjuvant (CFA). The hierarchy of anti-OVA antibody avidities was CFA > R <subscript>4</subscript> Pam <subscript>2</subscript> Cys = alum. Each of the three adjuvants facilitated IgG class-switching with significantly more IgG1 elicited by OVA when formulated with R <subscript>4</subscript> Pam <subscript>2</subscript> Cys. The effects of substituting naturally occurring L-stereoisomers of the cationic residues within R <subscript>4</subscript> Pam <subscript>2</subscript> Cys with D-stereoisomers revealed that substitution did not affect the ability of R <subscript>4</subscript> Pam <subscript>2</subscript> Cys to stimulate dendritic cell maturation or its ability to elicit antibody production when used as an adjuvant. Minor detrimental effects were, however, observed in the ensuing CD8 <superscript>+</superscript> T cell responses suggesting that the use of D-amino acids affects antigen processing and presentation pathways involved in generation of cell-mediated immunity at least when facilitated through TLR2. Both D- and L-forms were found to be resistant to digestion by trypsin, indicating resistance of the branched structure to protease activity.
- Subjects :
- Animals
Female
Immunoglobulin G immunology
Mice
Mice, Inbred BALB C
Static Electricity
Structure-Activity Relationship
Toll-Like Receptor 2 immunology
CD8-Positive T-Lymphocytes immunology
Lipopeptides chemical synthesis
Lipopeptides chemistry
Lipopeptides immunology
Lipopeptides pharmacology
Ovalbumin chemistry
Ovalbumin immunology
Ovalbumin pharmacology
Toll-Like Receptor 2 agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1438-2199
- Volume :
- 49
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Amino acids
- Publication Type :
- Academic Journal
- Accession number :
- 28718065
- Full Text :
- https://doi.org/10.1007/s00726-017-2466-6