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S. W. McPherson, N. D. Heuss, C. Norbury, M. Theoret, D. Palmer, N. Restifo, D. S. Gregerson; BG2: Analysis of a T Cell Receptor Transgenic B6 Mouse Specific for B-Galactosidase. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5924.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we developed and characterized a T cell receptor (TCR) transgenic (Tg) B10.A mouse (bgalTCR) specific for b-galactosidase (bgal) to study the immune response to bgal when expressed as a retinal neo-self antigen (Ag). Using these mice we observed mechanisms of immune regulation induced by retinal Ags that were different than those reported using the 3A9 TCR Tg T cell/retinal hen egg lysozyme Ag system (McPherson, et al., J. Immunol. 182; Ham, et al., IOVS. 45; and Lambe, et al., J. Immunol. 178). In order to confirm the validity of our model we examined the immune response to retinal bgal using a different TCR Tg mouse. Here we report on a B6 TCR-Tg mouse specific for bgal; BG2.
A TCR Tg mouse on the B6 MHC background specific for a class II MHC restricted (CD4+ T cell) epitope of bgal was developed. Identification of the BG2 T cell epitope was done by in vitro proliferation and cytokine assays using overlapping peptides of bgal. Pathogenicity of the epitope was assayed in adaptive transfer of peptide-stimulated BG2 T cells. The regulatory T cell (Treg) immune regulation induced by retinal expression of bgal was analyzed by comparing the DTH (ear swelling) response of BG2 mice to B6arrbgal (Tg photoreceptor cell bgal expression) x BG2 double Tg mice.
Two peptides of bgal containing the common epitope of SVTLPAASHAI induced proliferation and production of IL-2, IFNg, and TNFa by BG2 T cells. Adoptive transfer of BG2 T cells stimulated with either peptide induced experimental autoimmune uveoretinitis (EAU) in B6arrbgal mice. B6arrbgal x BG2 double Tg mice exhibited reduced ear swelling compared to BG2 mice indicative of bgal-specific regulatory immune response associated with its expression in photoreceptor cells. All of these results are similar to those obtained using bgalTCR mice.
We have developed and characterized the immune response of a B6 TCR Tg mouse specific for a retinal neo-self antigen. The fact that we obtained similar results with both our B10.A and B6 TCR Tg mice supports our findings that photoreceptor cell Ags induce a Treg mediated immune regulation.
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