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Receptor-linked antigen delivery system. Importance of autologous alpha 2-macroglobulin in the development of peptide
S Mitsuda1, T Nakagawa, H Nakazato
1Department of Biological Sciences, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
We have hijacked a process of the receptor-mediated endocytosis to transport peptide antigens into antigen presenting cells (APCs) for the purpose of increasing the level of antigen presentation (named Receptor-Linked Antigen Delivery System (R-LADS)). By coupling an endogenous plasma proteinase inhibitor alpha 2-macroglobulin (alpha 2M) to a synthetic peptide having a partial sequence of HIV-1 envelope protein, alpha 2M was made to carry the peptide into APCs as a part of the normal alpha 2M cycle, which resulted in an increased production of specific antibodies against the peptide (Mitsuda, S., Nakagawa, T., Osada, T., Shimamoto, T., Nakazato, H. and Ikai, A. (1993) Biochem. Biophys. Res. Commun. 194, 1155-1160). We demonstrate here that this procedure becomes a more efficient tool for antibody production when autologous transporter protein was used. By using murine alpha 2M (m alpha 2M) instead of heterologous human alpha 2M (h alpha 2M) when mice were experimental animals, we were able to dramatically enhance the production level of anti-HIV-1 peptide antibodies and shorten the period which is needed for antibody production. We aim to develop effective peptide vaccines by further improving this system.
We have hijacked a process of the receptor-mediated endocytosis to transport peptide antigens into antigen presenting cells (APCs) for the purpose of increasing the level of antigen presentation (named Receptor-Linked Antigen Delivery System (R-LADS)). By coupling an endogenous plasma proteinase inhibitor alpha 2-macroglobulin (alpha 2M) to a synthetic peptide having a partial sequence of HIV-1 envelope protein, alpha 2M was made to carry the peptide into APCs as a part of the normal alpha 2M cycle, which resulted in an increased production of specific antibodies against the peptide (Mitsuda, S., Nakagawa, T., Osada, T., Shimamoto, T., Nakazato, H. and Ikai, A. (1993) Biochem. Biophys. Res. Commun. 194, 1155-1160). We demonstrate here that this procedure becomes a more efficient tool for antibody production when autologous transporter protein was used. By using murine alpha 2M (m alpha 2M) instead of heterologous human alpha 2M (h alpha 2M) when mice were experimental animals, we were able to dramatically enhance the production level of anti-HIV-1 peptide antibodies and shorten the period which is needed for antibody production. We aim to develop effective peptide vaccines by further improving this system.