Epitopes described in "Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells."

Article Authors:Jianmei W Leavenworth; Xiaolei Tang; Hye-Jung Kim; Xiaoyang Wang; Harvey Cantor
Article Title:Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells.
Reference Detail
Reference ID:1025625
Abstract:Current therapies to treat autoimmune disease focus mainly on downstream targets of autoimmune responses, including effector cells and cytokines. A potentially more effective approach would entail targeting autoreactive T cells that initiate the disease cascade and break self tolerance. The murine MHC class Ib molecule Qa-1b (HLA-E in humans) exhibits limited polymorphisms and binds to 2 dominant self peptides: Hsp60(p216) and Qdm. We found that peptide-induced expansion of tetramer-binding CD8(+) Tregs that recognize Qa-1-Hsp60(p216) but not Qa-1-Qdm strongly inhibited collagen-induced arthritis, an animal model of human rheumatoid arthritis. Perforin-dependent elimination of autoreactive follicular Th (T(FH)) and Th17 cells by CD8(+) Tregs inhibited disease development. Infusion of in vitro-expanded CD8(+) Tregs increased the efficacy of methotrexate treatment and halted disease progression after clinical onset, suggesting an alternative approach to this first-line treatment. Moreover, infusion of small numbers of Qa-1-Hsp60(p216)-specific CD8(+) Tregs resulted in robust inhibition of autoimmune arthritis, confirming the inhibitory effects of Hsp60(p216) peptide immunization. These results suggest that strategies designed to expand Qa-1-restricted (HLA-E-restricted), peptide-specific CD8(+) Tregs represent a promising therapeutic approach to autoimmune disorders.
Affiliations:Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Reference Type:Literature
PubMed ID:23376792
Journal:J Clin Invest
Journal Volume:123
Article Pages:1382-9
Journal ISSN:0021-9738
Article Chemical List:Chaperonin 60;Histocompatibility Antigens Class I;Hspd1 protein, mouse;Interleukin-15;Mitochondrial Proteins;Peptide Fragments;Peptides;Q surface antigens;Qdm protein, mouse;Perforin;Methotrexate
Article MeSH List:Animals; Arthritis, Experimental(immunology; prevention & control); CD8-Positive T-Lymphocytes(immunology; physiology; transplantation); Cells, Cultured; Chaperonin 60(genetics; immunology); Histocompatibility Antigens Class I(immunology); Humans; Immunization; Interleukin-15(metabolism); Male; Methotrexate(pharmacology); Mice; Mice, Inbred C57BL; Mitochondrial Proteins(genetics; immunology); Mutation, Missense; Peptide Fragments(immunology); Peptides(immunology); Perforin(metabolism); T-Lymphocytes, Regulatory(immunology; physiology; transplantation); Th17 Cells(immunology)
Curation Last Updated:2015-07-30 20:47:10