Polymerisation of a T cell epitope with an immunostimulatory C3d peptide sequence enhances antigen specific T cell responses
AuthorO'Brien-Simpson, Neil M.; Attard, Troy J.; Zheng, Baihui; Walsh, Katrina A.; Reynolds, Eric C.
Source TitleInternational Journal of Peptide Research and Therapeutics
University of Melbourne Author/sO'Brien-Simpson, Neil; Attard, Troy; ZHENG, BAIHUI; Walsh, Katrina; Reynolds, Eric
Melbourne Dental School
Oral Health CRC, Melbourne Dental School
Document TypeJournal Article
CitationsO'Brien-Simpson, N. M., Attard, T. J., Zheng, B., Walsh, K. A., & Reynolds, E. C. (2013). Polymerisation of a T cell epitope with an immunostimulatory C3d peptide sequence enhances antigen specific T cell responses. International Journal of Peptide Research and Therapeutics, 19(1), 81-91.
Access StatusOpen Access
NHMRC Grant codeNHMRC/1008106
© Springer Science+Business Media New York 2013
The research outputs in this collection have been funded in whole or in part by the National Health and Medical Research Council (NHMRC)
The complement protein C3d and C3d derived peptides that bind CD21 are known to enhance immunity to co-immunised antigens. In this study we have synthesised the minimal CD21 binding sequence of C3d (1227LYNVEA 1232) as mono, di and tri tandem repeats and derivatised the N-terminus with an acryloyl moiety. These acryloyl-(C3d)n peptides were co-polymerised with a acryloyl-T cell epitope (PAS1K) from the Porphyromonas gingivalis antigen the RgpA–Kgp proteinase–adhesin complex. The ability of C3d containing polymers to enhance T cell immunity in vitro and in vivo was evaluated. When used to stimulate in vitro PAS1K-primed or RgpA–Kgp complex-primed T cells the C3d containing PAS1K polymers induced a mixed and significantly (p\0.05) higher IL-4 and IFNc T cell response compared to that induced by the PAS1K peptide or polymer. PAS1K polymers containing tandem repeats of C3d induced a significantly (p\0.05) stronger maximal proliferative response, at the same antigenic dose, compared to that induced by the PAS1K peptide or polymer. When used as immunogens to prime T cells all of the C3d containing PAS1K polymers induced a dominant IFNc T cell response and reduced the antigen dose required for maximal proliferation 150-fold compared to that required for the PAS1K-peptide or polymer primed T cells. In conclusion, the 6 residue sequence LYNVEA from C3d is sufficient to enhance immunity to an antigen and that the effect is more pronounced when C3d is part of the immunising antigen rather than an in vitro stimulating antigen.
KeywordsC3d complement; peptide synthesis; peptide polymers; T cell immune responses
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