In vivo induction of tolerance by an lg peptide is not affected by the deletion of FcR or a mutated lgG Fc fragment

Moustapha El-Amine, Jennifer A. Hinshaw, David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


To induce tolerance to a variety of epitopes, we have designed a gene therapy approach in which peptides or antigens are expressed in frame on a soluble IgG fusion protein scaffold and delivered via retroviral gene therapy in B cells in vivo. Initially, tolerance to the λ repressor cl sequence p1-102 or its immunodominant epitopes (e.g. p12-26 or p73-88) was elicited in both T cells and B cells when lipopolysaccharide (LPS) blasts are transduced and injected into naive or even primed recipients. While a role of secreted Ig fusion protein in this process is not clear, we have previously demonstrated the importance of antigen presentation on MHC class II of B cell antigen-presenting cells (APC) for tolerance induction. To further examine the role of the lg and especially of the Fc portion of the lgG in tolerogenesis, we transduced LPS blasts from FcRγII-/-, FcγRI-/-, FcγRIII-/-, FcR-/- or naive mice with retroviral vectors expressing lgG1-102, ΔlgG1-102 (mutated construct on position 297 of the Fc portion) or lgG12-26. When these transduced LPS blasts from FcR knockout mice were injected into normal (or knockout) syngeneic recipient mice, they induced tolerance both to the immunodominant epitopes and the full-length protein in that the antibody responses to the immunodominant epitopes were reduced. In this paper, we show that this tolerance resides at both the T and B cell level. Moreover, mutation of residue 297, which affects lgG functions including FcR binding, did not alter the tolerogenicity of the construct. These results suggest that the Fc portion of the lgG molecules is not required for humoral nor for cellular tolerance induction using the lgG-antigen tolerogens.

Original languageEnglish
Pages (from-to)761-766
Number of pages6
JournalInternational Immunology
Issue number7
StatePublished - 2002
Externally publishedYes


  • B cell
  • FcR
  • Gene therapy
  • Retroviral vector
  • T cell
  • Tolerance
  • lgG-antigen


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