Novel function of complement C3d as an autologous helper T-cell target

Immunology and Cell Biology
Paul M KnopfAnne S De Groot

Abstract

The C3d fragment of complement component C3 has been shown to enhance immune responses to antigens that lack T-cell epitopes such as bacterial polysaccharides. C3d binds to the B-cell complement receptor 2 (CR2 or CD21); this binding serves as a co-activation signal to the B cell when the polysaccharide antigen portion binds simultaneously to the B-cell receptor (surface Ig). Bringing together receptor-associated signal transduction molecules CD19 and Igalpha/beta, respectively, results in a lower threshold of activation. Paradoxically, C3d has also been shown to enhance antibody titers in the CD21 knockout (KO) mouse model as well as increase Th1 and Th2 cytokine secretion, suggesting that that an auxiliary CR2-independent pathway of immune activation may exist. We hypothesized that in addition to its molecular adjuvant property that enhances signal 1 during B-cell activation (co-signal 1), C3d also contains T-cell epitopes that are able to stimulate autoreactive C3d peptide-specific helper T cells which we term 'co-signal 2'. Using the EpiMatrix T-cell epitope-mapping algorithm, we identified 11 putative T-cell epitopes in C3d, a very high epitope density for a 302 amino-acid sequence. Eight of these epitope candidates were s...Continue Reading

References

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Citations

Nov 12, 2014·Immunology and Cell Biology·Anne S De GrootPaul M Knopf
Jan 30, 2010·American Journal of Rhinology & Allergy·Rodney J SchlosserCarl Atkinson
Feb 2, 2019·Expert Review of Vaccines·Hannah G KellyAdam K Wheatley
May 16, 2013·Organic & Biomolecular Chemistry·Lorena Simón-GraciaMiriam Royo
Aug 1, 2020·Frontiers in Immunology·Jack MellorsMiles Carroll
May 5, 2017·JCI Insight·Jeffrey L PlattMarilia Cascalho
Apr 23, 2020·Advanced Drug Delivery Reviews·Farjana KhatunRachel J Stephenson
Aug 1, 2021·Journal of Biomedical Materials Research. Part a·Feiyang CaiXing Jiang

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