Modulation of immunogenicity and antigenicity of proteins by maleylation to target scavenger receptors on macrophages

R. Abraham, Nagendra Singh, A. Mukhopadhyay, S. K. Basu, V. Bal, S. Rath

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Abstract

We have maleylated proteins to target macrophage-specific scavenger receptors and have used this system to study changes in the epitopes and immunogenicity of such proteins. We show that maleylation of diphtheria toxoid (DT) induces targeting to macrophage scavenger receptors and enhances its immunogenicity. DT does not evoke detectable serum Ab responses upon injection as soluble protein. However, maleylated DT (mDT) does generate a significant Ab response. Furthermore, immunization with soluble mDT leads to a better T cell proliferative response in vitro than immunization with DT can generate, thereby demonstrating that maleylation leads to enhanced T cell immunogenicity in vivo. We also find that maleylation disrupts the native B cell epitopes of DT and creates new epitopes, because antisera to DT and mDT do not cross-react. At least some of the new epitopes generated are maleylation specific, because antisera against various maleylated proteins do cross-react. In contrast, maleylation does not significantly modify the repertoire of T cell epitopes generated from DT, because T cells generated by either DT or mDT immunization are cross-reactive, and both DT and mDT can stimulate T cells that are specific for a single synthetic DT peptide. Maleylated proteins are better presented in vitro than are their native counterparts, and this enhancement of presentation is blocked by unrelated maleylated proteins. These results suggest that Ags targeted to scavenger receptors on macrophages by maleylation are better presented to T cells and are immunogenic in rive without adjuvant.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Immunology
Volume154
Issue number1
StatePublished - Jan 1 1995

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Diphtheria Toxoid
Scavenger Receptors
Proteins
T-Lymphocytes
Epitopes
Immunization
Immune Sera
B-Lymphocyte Epitopes
T-Lymphocyte Epitopes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Modulation of immunogenicity and antigenicity of proteins by maleylation to target scavenger receptors on macrophages. / Abraham, R.; Singh, Nagendra; Mukhopadhyay, A.; Basu, S. K.; Bal, V.; Rath, S.

In: Journal of Immunology, Vol. 154, No. 1, 01.01.1995, p. 1-8.

Research output: Contribution to journalArticle

Abraham, R. ; Singh, Nagendra ; Mukhopadhyay, A. ; Basu, S. K. ; Bal, V. ; Rath, S. / Modulation of immunogenicity and antigenicity of proteins by maleylation to target scavenger receptors on macrophages. In: Journal of Immunology. 1995 ; Vol. 154, No. 1. pp. 1-8.
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