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Murine CR1/2 Targeted Antigenized Single-Chain Antibody Fragments Induce Transient Low Affinity Antibodies and Negatively Influence an Ongoing Immune Response

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Current Topics in Innate Immunity

Abstract

We have generated a single-chain antibody which recognizes murine CR1/2 and carries a genetically fused influenza hemagglutinin derived peptide. Theoretically such a construct is able to crosslink the B cell antigen receptor and CR1/2 on peptide specific B cells. The construct was able to reach its CR1/2 positive target cells, yet intraperitoneal delivery of the construct elicited an IgM response only slightly exceeding that induced by the free peptide. Providing T cell help by the injection of peptide specific lymphocytes did not alter the response in essence, that is anti-peptide IgG was not detectable even after booster immunizations. When used as a booster vaccine following injection of the peptide in adjuvant, the construct even inhibited the development of IgG1 and IgG3 anti-peptide antibodies.

These data indicate that although targeting of antigen to CR1/2 on B cells can enhance transient proliferation or differentiation of antigen specific B cells it cannot induce strong, longlasting humoral immune responses. Furthermore, CR1/2 targeting constructs may negatively influence an ongoing immune reaction.

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References

  • Ahearn, J.M., Fischer, M.B., Croix, D., Goerg, S., Ma, M., Xia, J., Zhou, X., Howard, R.G., Rothstein, T.L., Carroll, M.C., 1996. Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity. 4, 251-262.

    Article  PubMed  CAS  Google Scholar 

  • Applequist, S.E., Dahlstrom, J., Jiang, N., Molina, H., Heyman, B., 2000. Antibody production in mice deficient for complement receptors 1 and 2 can be induced by IgG/Ag and IgE/Ag, but not IgM/Ag complexes. J. Immunol. 165, 2398-2403.

    PubMed  CAS  Google Scholar 

  • Baiu, D.C., Prechl, J., Tchorbanov, A., Molina, H.D., Erdei, A., Sulica, A., Capel, P.J., Hazenbos, W.L., 1999. Modulation of the humoral immune response by antibody-mediated antigen targeting to complement receptors and Fc receptors. J. Immunol. 162, 3125-3130.

    PubMed  CAS  Google Scholar 

  • Chen, Z., Koralov, S.B., Gendelman, M., Carroll, M.C., Kelsoe, G., 2000. Humoral immune responses in Cr2-/- mice: enhanced affinity maturation but impaired antibody persistence. J. Immunol. 164, 4522-4532.

    PubMed  CAS  Google Scholar 

  • Croix, D.A., Ahearn, J.M., Rosengard, A.M., Han, S., Kelsoe, G., Ma, M., Carroll, M.C., 1996. Antibody response to a T-dependent antigen requires B cell expression of complement receptors. J. Exp. Med. 183, 1857-1864.

    Article  PubMed  CAS  Google Scholar 

  • Dempsey, P.W., Allison, M.E., Akkaraju, S., Goodnow, C.C., Fearon, D.T., 1996. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science {%}19;271, 348-350.

    Article  Google Scholar 

  • Fearon, D.T., Carroll, M.C., 2000. Regulation of B lymphocyte responses to foreign and self-antigens by the CD19/CD21 complex. Annu. Rev. Immunol. 18, 393-422.

    Article  PubMed  CAS  Google Scholar 

  • Gaither, T.A., Vargas, I., Inada, S., Frank, M.M., 1987. The complement fragment C3d facilitates phagocytosis by monocytes. Immunology 62, 405-411.

    PubMed  CAS  Google Scholar 

  • Haas, K.M., Hasegawa, M., Steeber, D.A., Poe, J.C., Zabel, M.D., Bock, C.B., Karp, D.R., Briles, D.E., Weis, J.H., Tedder, T.F., 2002. Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responses. Immunity. 17, 713-723.

    Article  PubMed  CAS  Google Scholar 

  • Haas, K.M., Toapanta, F.R., Oliver, J.A., Poe, J.C., Weis, J.H., Karp, D.R., Bower, J.F., Ross, T.M., Tedder, T.F., 2004. Cutting edge: C3d functions as a molecular adjuvant in the absence of CD21/35 expression. J. Immunol. 172, 5833-5837.

    PubMed  CAS  Google Scholar 

  • Lou, D., Kohler, H., 1998. Enhanced molecular mimicry of CEA using photoaffinity crosslinked C3d peptide. Nat. Biotechnol. 16, 458-462.

    Article  PubMed  CAS  Google Scholar 

  • Molina, H., Holers, V.M., Li, B., Fung, Y., Mariathasan, S., Goellner, J., Strauss-Schoenberger, J., Karr, R.W., Chaplin, D.D., 1996. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc. Natl. Acad. Sci. U. S. A 93, 3357-3361.

    Article  CAS  Google Scholar 

  • Prechl, J., Tchorbanov, A., Horvath, A., Baiu, D.C., Hazenbos, W., Rajnavolgyi, E., Kurucz, I., Capel, P.J., Erdei, A., 1999. Targeting of influenza epitopes to murine CR1/CR2 using single-chain antibodies. Immunopharmacology 42, 159-165.

    Article  PubMed  CAS  Google Scholar 

  • Qin, D., Wu, J., Carroll, M.C., Burton, G.F., Szakal, A.K., Tew, J.G., 1998. Evidence for an important interaction between a complement-derived CD21 ligand on follicular dendritic cells and CD21 on B cells in the initiation of IgG responses. J. Immunol. 161, 4549-4554.

    PubMed  CAS  Google Scholar 

  • Rajnavolgyi, E., Horvath, A., Gogolak, P., Toth, G.K., Fazekas, G., Fridkin, M., Pecht, I., 1997. Characterizing immunodominant and protective influenza hemagglutinin epitopes by functional activity and relative binding to major histocompatibility complex class II sites. Eur. J. Immunol. 27, 3105-3114.

    Article  PubMed  CAS  Google Scholar 

  • Ross, T.M., Xu, Y., Bright, R.A., Robinson, H.L., 2000. C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge. Nat. Immunol. 1, 127-131.

    Article  PubMed  CAS  Google Scholar 

  • Ross, T.M., Xu, Y., Green, T.D., Montefiori, D.C., Robinson, H.L., 2001. Enhanced avidity maturation of antibody to human immunodeficiency virus envelope: DNA vaccination with gp120-C3d fusion proteins. AIDS Res. Hum. Retroviruses 17, 829-835.

    Article  PubMed  CAS  Google Scholar 

  • Villiers, M.B., Villiers, C.L., Laharie, A.M., Marche, P.N., 1999. Amplification of the antibody response by C3b complexed to antigen through an ester link. J. Immunol. 162, 3647-3652.

    PubMed  CAS  Google Scholar 

  • Whipple, E.C., Shanahan, R.S., Ditto, A.H., Taylor, R.P., Lindorfer, M.A., 2004. Analyses of the in vivo trafficking of stoichiometric doses of an anti-complement receptor 1/2 monoclonal antibody infused intravenously in mice. J. Immunol. 173, 2297-2306.

    PubMed  CAS  Google Scholar 

  • Wu, X., Jiang, N., Fang, Y.F., Xu, C., Mao, D., Singh, J., Fu, Y.X., Molina, H., 2000. Impaired affinity maturation in Cr2-/- mice is rescued by adjuvants without improvement in germinal center development. J. Immunol. 165, 3119-3127.

    PubMed  CAS  Google Scholar 

  • Wykes, M., Pombo, A., Jenkins, C., MacPherson, G.G., 1998. Dendritic cells interact directly with naive B lymphocytes to transfer antigen and initiate class switching in a primary T-dependent response. J. Immunol. 161, 1313-1319.

    PubMed  CAS  Google Scholar 

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Prechl, J. et al. (2007). Murine CR1/2 Targeted Antigenized Single-Chain Antibody Fragments Induce Transient Low Affinity Antibodies and Negatively Influence an Ongoing Immune Response. In: Lambris, J.D. (eds) Current Topics in Innate Immunity. Advances in Experimental Medicine and Biology, vol 598. Springer, New York, NY. https://doi.org/10.1007/978-0-387-71767-8_15

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