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Current Topics in Complement pp 249–264Cite as

A Minimum CR2 Binding Domain of C3d Enhances Immunity Following Vaccination

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Part of the book series: Advances in Experimental Medicine and Biology ((volume 586))

1. Abstract

The degradation product of the third (C3) complement component, C3d, links innate and adaptive immunity, and the covalent attachment of C3d to an antigen enhances antigen-specific immune responses. C3d has been hypothesized to enhance immunity by direct interaction with complement receptor 2 (CR2/CD21) on immune cells. However, the domains on C3d important for CR2 binding have been controversial, with various studies reaching contradictory conclusions. In addition, the concept of B-cell activation via CR2 by C3d has been questioned, since mice lacking CR2 still elicit C3d-enhanced immunity following vaccination. Therefore, the goal of this study was to determine if a peptide representing one of the proposed CR2 binding domains of C3d could substitute for the entire protein and enhance antigen-specific immunity. Mice (BALB/c) were vaccinated with the HIV-1 gp120 envelope glycoprotein (Envgp120) alone or fused to multiple copies of the murine C3d or a twenty-eight amino-acid peptide (P28) containing a minimum CR2 binding domain. Each immunogen was expressed from DNA plasmid in vivo or injected as purified recombinant protein. The fusion of the P28 peptide to Envgp120 enhanced both humoral and cell-mediated immune responses with similar efficiency as Envgp120 conjugated to C3d. The fusion of C3d or P28 to Envgp120 elicited higher-titer anti-Env specific antibody, enhanced avidity maturation of the elicited antibody, and elicited higher numbers of IFN-γ and IL-4 secreting cells compared to Envgp120 immunizations. This CR2-binding domain specific 28 amino acid peptide can substitute for the entire C3d molecule and enhance immunity. These results indicate that the adjuvant properties of C3d are associated with CR2 interaction.

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Authors and Affiliations

  1. Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, School of Medicine, Pittsburgh, PA, 15261, USA

    Joseph F. Bower & Ted M. Ross

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  1. Joseph F. Bower
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  1. University of Pennsylvania, Philadelphia, PA, 19107

    John D. Lambris Ph.D. (Professor of Pathology & Laboratory Medicine) (Professor of Pathology & Laboratory Medicine)

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Bower, J.F., Ross, T.M. (2006). A Minimum CR2 Binding Domain of C3d Enhances Immunity Following Vaccination. In: Lambris, J.D. (eds) Current Topics in Complement. Advances in Experimental Medicine and Biology, vol 586. Springer, Boston, MA. https://doi.org/10.1007/0-387-34134-X_17

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