Murine CR1/2 Targeted Antigenized Single-Chain Antibody Fragments Induce Transient Low Affinity Antibodies and Negatively Influence an Ongoing Immune Response
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.
KeywordsHumoral Immune Response Complement Receptor Affinity Maturation Booster Immunization Cell Antigen Receptor
Unable to display preview. Download preview PDF.
- 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar